ORCID Profile
0000-0002-7686-4505
Current Organisation
Garvan Institute of Medical Research
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Publisher: Springer Science and Business Media LLC
Date: 07-07-2021
DOI: 10.1186/S12920-021-01029-3
Abstract: Breast cancer (BC) is the most invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered critical nutrition that many cancer cells, particularly BC cells, are dependent on it for growth and proliferation. Therefore, targeting glutamine metabolism, especially enzymes that are related to this pathway, can be beneficial to design anti-cancer agents. Recent evidence has shown that microRNAs (miRNAs), with a short length and single-strand properties, play a prominent role in regulating the genes related to glutamine metabolism, which may control the development of cancer. In silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism. The expression level of these two miRNAs was evaluated in eighty BC tissues and normal adjacent tissues. Furthermore, GSE38167, GSE38867, GSE42128, GSE45666, and GSE53179 were employed from gene expression omnibus (GEO). The Limma package was utilized to identify differentially expressed miRNAs (DEMs) of mentioned datasets to evaluate miR-513c and miR-3163 expression. Further, in silico analysis was utilized to predict the potential biological processes and molecular pathways of miR-513c and miR-3163, based on their target genes. In silico studies revealed top categories of biological processes and cellular pathways that might play a critical role in metabolism reprogramming and cancer development and were target genes for miR-513c and miR-3163. The current study showed that miR-513c ( p value = 0.02062 and FC = − 2.3801) and miR-3163 ( p value = 0.02034 and FC = − 2.3792) were downregulated in tumor tissues compared to normal adjacent tissues. The analysis of GEO microarray datasets showed that miR-513c was downregulated in GSE38167, GSE38867, GSE42128, GSE45666 and GSE53179, whereas there was a significant downregulation of miR-3163 in only two studies, including GSE38867 and GSE42128 that they were in accordance with our experimental results. Furthermore, the subgroup analysis did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history of cancer, and abortion history. MiR-513c and miR-3163 were downregulated in BC tissues, which might serve as tumor suppressors. They are suggested as potential therapeutic targets for patients with BC.
Publisher: Bentham Science Publishers Ltd.
Date: 06-2021
DOI: 10.2174/1871520620666200903145939
Abstract: Cisplatin has a broad-spectrum antitumor activity and is widely used for the treatment of various malignant tumors. However, acquired or intrinsic resistance of cisplatin is a major problem for patients during the therapy. Recently, it has been reported Cancer Stem Cell (CSC)-derived drug resistance is a great challenge of tumor development and recurrence therefore, the sensitivity of Breast Cancer Stem Cells (BCSCs) to cisplatin is of particular importance. Increasing evidence has shown that there is a relationship between cisplatin resistance/sensitivity genes and related miRNAs. It is known that dysregulation of relevant miRNAs plays a critical role in regulating target genes of cisplatin resistance/sensitivity in various pathways such as cellular uptake/efflux, Epithelial-Mesenchymal Transition (EMT), hypoxia, and apoptosis. Furthermore, the efficacy of the current chemotherapeutic drugs, including cisplatin, for providing personalized medicine, can be improved by controlling the expression of miRNAs. Thus, potential targeting of miRNAs can lead to miRNA-based therapies, which will help overcome drug resistance and develop more effective personalized anti-cancer and cotreatment strategies in breast cancer. In this review, we summarized the general understandings of miRNAregulated biological processes in breast cancer, particularly focused on the role of miRNA in cisplatin resistance/ sensitivity.
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.MICPATH.2018.11.031
Abstract: Recent studies have been considered to symbiotic interactions of the human gastrointestinal microbiota and human lifestyle-related disorders. The human gastrointestinal microbiota continuously stimulates the immune system against opportunistic and pathogen bacteria from infancy. Changes in gastrointestinal microbiota have been associated with numbers of human diseases such as allergic diseases, autoimmune encephalitis, atherosclerosis, colorectal cancer, obesity, diabetes etc. In this review article, we evaluate studies on the roles of human gastrointestinal microbiota and interference pathogenicity in allergic diseases, obesity, and diabetes. Several studies indicated association between allergic diseases and changes in bacterial balance such as increased of Clostridium spp., some species of Bifidobacterium spp., or decreased of Bacteroidetes phylum and some species of Bifiobacterium spp. and production of specific short-chain fatty acids due to food type, delivery modes of infant, infant evolvement environment and time of getting bacteria at an early-life age. In addition, obesity and diabetes are associated with food type, production of short chain fatty acids undergo fermentation of the intestinal microbiota, metabolic endotoxemia, endocannabinoid system and properties of the immune system. Well-characterized underlying mechanisms may provide novel strategies for using prebiotic and probiotic to prevent and treatment of allergic diseases, obesity, diabetes, and other lifestyle-related disorders.
Publisher: Elsevier BV
Date: 05-2019
DOI: 10.1016/J.GENE.2019.02.074
Abstract: Coronary artery disease (CAD) is primarily caused by atherosclerosis, which is a series of chronic inflammatory processes leading to the initiation and progression of vascular endothelial cell injury enhancing plaque formation. As critical components of the immune system, peripheral blood mononuclear cells (PBMCs) actively cross-talk with pathophysiological conditions induced by endothelial cell injury, reflecting in altered PBMC expression pattern. This study explored PBMC expression levels of miR-21, miR-25 and PTEN in patients with angiographically proven significant coronary stenosis (the CAD group), patients with insignificant coronary stenosis (the ICAD group) and healthy subjects, and assessed potentials of PBMC expressions in discriminating groups of study subjects. In-silico analysis was also performed to obtain insights into CAD-related pathways and biological processes that may be influenced by altered miRNA expressions. A reduced level of PBMC miR-21 was observed in the ICAD group compared to the CAD group (P: 0.004) or healthy controls (P: 0.0001). PBMC miR-21 level was negatively correlated with the PTEN expression (Spearman r: -0.43, P: 3.9e-09). The PTEN expression was increased in the CAD or ICAD group compared to the control group (CAD vs. controls P: 0.0003, ICAD vs. controls P: 0.03). A stepwise increase in PBMC miR-25 levels was observed from healthy controls to ICADs and CAD patients (Kruskal-Wallis P: 7.68e-12). PBMC gene expressions had reasonable power to discriminate between pairs of study groups. PBMC miR-21 levels were able to discriminate ICADs from both CADs and controls and miR-25 levels had potentials to differentiate among all pairs of study groups (i.e. CADs-ICADs, CADs-controls, CADs-all other subjects, ICADs-controls). PBMC PTEN expression was able to discriminate patients with CAD or ICAD from control subjects. Overrepresentation enrichment analysis of experimentally validated targets of miR-21 and miR-25 highlighted key biological processes and pathways, such as "angiogenesis" and "leukocyte cell-cell adhesion", that may be influenced by dysregulation of PBMC miR-21 and miR-25. In conclusion, these findings suggest that patients with insignificant coronary stenosis may have a distinct PBMC miRNA expression profile than those with significant stenosis or healthy controls.
Publisher: Elsevier BV
Date: 05-2018
DOI: 10.1016/J.GENE.2018.02.032
Abstract: The purpose of the present study was to evaluate microRNA-140-3p expression level in breast cancer patients in comparison to healthy controls. Serum microRNA-140-3p level was quantified by realtime quantitative reverse transcription PCR in 40 women with breast cancer and 40 healthy subjects. Serum microRNA-140-3p level in patients compared to healthy subjects was significantly up-regulated (P = 0.01). MicroRNA-140-3p had a good diagnostic accuracy for discrimination of the two groups (AUC = 0.667 sensitivity = 70% specificity = 50%). Serum microRNA-140-3p level was overexpressed in premenopausal patients who were ≤48 years old. ROC curve showed a similar pattern again (AUC = 0.690 sensitivity = 73% specificity = 50%). microRNA-140-3p has the potential for detection of breast cancer, especially in premenopausal and in ≤48 years old women.
Publisher: SAGE Publications
Date: 24-04-2018
Abstract: Epidemiological and experimental literature indicates that the risk of breast cancer incidence is strongly linked to hormone-dependent factors, including reproductive history and obesity. However, the molecular mechanisms underlying the association between these factors and breast cancer risk are poorly understood. The aim of this study, therefore, was to determine whether obesity and reproductive history are associated with expression levels of two breast cancer-related long non-coding RNAs (lncRNAs), namely ZFAS1 and SRA1 in cancer-free breast tissues of women. In the current research, 145 healthy women were recruited, and the quantitative expression levels of the two lncRNAs were determined through qPCR assay after gathering the mammoplasty breast tissue s les. It was found that women with body mass index (BMI)≥30 kg/m 2 and BMI 25–29 kg/m 2 show a low expression of ZFAS1 compared to the BMI kg/m 2 ( P=0.031 and P=0.027, respectively). Then, the correlation analysis disclosed a negative correlation of ZFAS1 low expression with increasing BMI (r=−0.194, P=0.019). Interestingly, this analysis demonstrated a negative correlation between low expression of the ZFAS1 and high BMI in women with menarche age below 14 (r=−221 P=0.028). Lastly, it was also revealed that there was a negative association of the low expression level of ZFAS1 with increasing BMI in women through regression models (B=−0.048, P=0.019). These findings suggest interesting clues about the links between high BMI and the expression levels of ZFAS1 in non-diseased breasts that may help us better understand the underlying mechanisms through which obesity contributes to breast carcinogenesis. However, such results need more validations in future research.
Publisher: Springer Science and Business Media LLC
Date: 26-11-2019
Publisher: Research Square Platform LLC
Date: 03-12-2020
DOI: 10.21203/RS.3.RS-28926/V2
Abstract: Background: Breast cancer (BC) is the most common invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered a critical nutrition for tumor cell growth and therefore, targeting glutamine metabolism, especially Glutaminase, which catalyzed the conversion of glutamine to glutamate can be beneficial to design anti-cancer agents. Recently, evidence has shown that miRNAs with short length and single strand properties play a significant role in regulating the genes related to glutamine metabolism and may control the development of cancer. Methods: Since, in-silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism, the expression level of these two miRNAs was evaluated in eighty BC tissues and margin tissues. The data were analyzed to evaluate the correlation between expression level of these miRNAs and patient’s characteristics such as abortion history, family history, and age. Furthermore, in-silico analysis was applied to predict the potential biological processes and molecular pathways of miR-513c and miR-3163 based on its gene targets. Results: In-silico studies revealed the top categories of biological processes and pathways that play a critical role in cancer development were target genes for miR-513c and miR-3163. The current study showed that miR-513c (P-value= 0.02062 and fold change= -2.3801) and miR-3163 (P-value= 0.02034 and fold change= -2.3792) were downregulated in tumor tissues compared to margin tissues. Furthermore, the subgroup studies did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history cancer, and abortion. Conclusion: Based on our data, miR-513c and miR-3163 may be offered as a potential diagnosis and therapeutic targets for patients with BC.
Publisher: MDPI AG
Date: 12-01-2019
DOI: 10.3390/IJMS20020293
Abstract: Recently extensive focus has been concentrated on the role of miRNAs in the initiation and progression of cardio-cerebrovascular diseases (CCDs) which constitute a range of conditions including cardiovascular diseases (CVDs, especially coronary artery disease (CAD)), congenital heart disease (CHD) and cerebrovascular diseases (CBVDs, especially the ischemic stroke (IS)). An increasing number of studies are evaluating the association between different miRNA polymorphisms and risk of CCDs, but results have been inconclusive. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and risk of CCDs. PubMed, Embase, Scopus, and Web of Science were queried to identify eligible articles. Odds ratios and 95% confidence intervals were used to assess the association of miRNA polymorphisms with CCD susceptibility. A total of 51 eligible articles evaluating the association of 31 miRNA polymorphisms were identified. Meta-analysis was performed for six miRNA polymorphisms. miR-146a rs2910164 (30 studies: 13,186 cases/14,497 controls), miR-149 rs2292832 (Nine studies: 4116 cases/3511 controls), miR-149 rs71428439 (Three studies: 1556 cases/1567 controls), miR-196a2 rs11614913 (20 studies: 10,144 cases/10,433 controls), miR-218 rs11134527 (Three studies: 2,322 cases/2,754 controls) were not associated with overall CCD. miR-499 rs3746444 was associated with CCD (20 studies: 9564 cases/8876 controls). In the subgroups, rs2910164 and rs3746444 were only associated with CVDs, especially CAD. In conclusion, the results support the existence of a role for miR-146a rs2910164 and miR-499 rs3746444 in determining susceptibility to CCDs, especially CAD.
Publisher: Wiley
Date: 31-01-2022
DOI: 10.1002/JCLA.24263
Abstract: Breast cancer (BC) is one of the leading causes of death among women around the world. Circular RNAs (circRNAs) are a newly discovered group of non‐coding RNAs that their roles are being investigated in BC and other cancer types. In this study, we evaluated the association of hsa_circ_0005986 and hsa_circ_000839 in tumor and adjacent normal tissues of BC patients with their clinicopathological characteristics. Total RNA was extracted from tumors and adjacent non‐tumor tissues by the Trizol isolation reagent, and cDNA was synthesized using First Strand cDNA Synthesis Kit (Thermo Scientific). The expression level of hsa_circ_0005986 and hsa_circ_000839 was quantified using RT‐qPCR. Online in silico tools were used for identifying potentially important competing endogenous RNA (ceRNA) networks of these two circRNAs. The expression level of hsa_circ_0005986 and hsa_circ_000839 was lower in the tumor as compared to adjacent tissues. The expression level of hsa_circ_0005986 in the patients who had used hair dye in the last 5 years was significantly lower. Moreover, a statistically significant negative correlation between body mass index (BMI) and hsa_circ_000839 expression was observed. In silico analysis of the ceRNA network of these circRNAs revealed mRNAs and miRNAs with crucial roles in BC. Downregulation of hsa_circ_000839 and hsa_circ_0005986 in BC tumors suggests a tumor‐suppressive role for these circRNAs in BC, meriting the need for more experimentations to delineate the exact mechanism of their involvement in BC pathogenesis.
Publisher: Informa UK Limited
Date: 06-2020
DOI: 10.2147/IDR.S238446
Publisher: Wiley
Date: 07-09-2017
DOI: 10.1002/JCP.26116
Abstract: Breast cancer (BC) is the most prevalent cancer in women worldwide. Although extensive studies are ongoing concerning its intricate molecular mechanisms, development of novel therapies and more accurate diagnostic and prognostic approaches is still a challenge. Epithelial–mesenchymal transition (EMT) enables the invasion of metastatic cancer cells and has recently been highlighted in a Cancer Stem Cell (CSC) model of BC. Epigenetic events as well as miRNA expression are the master regulators of tumorigenesis and add a further layer to the complexity of BC pathogenesis. The miRNAs are related to epigenetic event and additionally affect epigenetic pathways. Recent evidence demonstrates that epigenetic mechanisms such as DNA methylation may control miRNA expression. Because each miRNA may regulate several target genes, dysregulation of miRNA caused by aberrant DNA methylation patterns of the locus may influence important downstream pathways. Furthermore, some miRNAs is believed to regulate important DNA methylator factors. Any disruption or modification of this intricate network can contribute to the disease process thus, it is essential to understand these changes. Advancements in new sequencing technologies to detect DNA methylation patterns has provided the opportunity to determine differentially methylated regions (DMRs) of the miRNA locus and their effect on expression profiles to improve BC diagnosis and treatment. The current review examines the interplay of DNA methylation mechanisms and miRNA function in invasive tumorigenesis, specifically EMT and CSC of BC, to highlight its potential for advancements on BC etiology, diagnosis, and therapy.
Publisher: Elsevier BV
Date: 06-2020
Publisher: CMB Association
Date: 20-11-2015
Publisher: Elsevier BV
Date: 10-2021
DOI: 10.1016/J.YEXMP.2021.104664
Abstract: MicroRNAs (miRNAs) have emerged as a critical component of regulatory networks that modulate and fine-tune gene expression in a post-transcriptional manner. The microRNA-196 family is encoded by three loci in the human genome, namely hsa-mir-196a-1, hsa-mir-196a-2, and hsa-mir-196b. Increasing evidence supports the roles of different components of this miRNA family in regulating key cellular processes during differentiation and development, ranging from inflammation and differentiation of stem cells to limb development and remodeling and structure of adipose tissue. This review first discusses about the genomic context and regulation of this miRNA family and then take a bird's eye view on the updated list of its target genes and their biological processes to obtain insights about various functions played by members of the microRNA-196 family. We then describe evidence supporting the involvement of the human microRNA-196 family in regulating critical cellular processes both in physiological and non-malignant inflammatory conditions, highlighting recent seminal findings that carry implications for developing novel therapeutic or diagnostic strategies.
Publisher: Informa UK Limited
Date: 07-04-2019
DOI: 10.1080/01635581.2019.1599968
Abstract: In this study, we explored whether co-nanoencapsulated Curcumin (Cur) and Chrysin (Chr), natural herbal compounds with antitumor activities, regulate miR-132 and miR-502c and their downstream targets, leading to the synergistic growth inhibition in MDA-MB-231 breast cancer cells. For this purpose, Cur and Chr were co-encapsulated into PLGA-PEG nanoparticles (NPs) and characterized through DLS, FTIR and FE-SEM. MTT assay and cell cycle arrest analysis revealed that CurChr-loaded NPs had a considerable synergistic cytotoxicity against MDA-MB-231 cells with more cell accumulation in G2/M phase compared to the other groups. In addition, highest percentage of cell apoptosis was acquired in cells treated with CurChr-loaded NPs according to apoptosis analysis. Real-time PCR findings revealed that co-encapsulated form of Cur and Chr than free combination could further upregulate miR-132 and miR-502c expression (
Publisher: Elsevier BV
Date: 09-2021
DOI: 10.1016/J.PRP.2021.153560
Abstract: Esophageal Cancer is known as one of the deadliest cancers worldwide with the squamous cell carcinoma (ESCC) being the predominant subtype. There is a growing body of evidence linking the dysregulated microRNA (miRNA) pathway of immune cells to the progression of several tumors. In a previous study, we investigated molecular alterations pertaining to miR-146a and some components of NF-kB signaling pathway and proposed a possible immune downregulatory mechanism in peripheral blood mononuclear cells (PBMCs) of ESCC patients. Here, we further scrutinized other components of this pathway by evaluating PBMC levels of miR-146b, TLR4, IL10, and TNFA. Gene expressions were quantified using RT-qPCR assays. To prevent the vulnerability of results to the expression instability of reference genes, nine additional transcripts were quantified, and stable reference genes for normalizing qPCR data were identified using the NormFinder and the geNorm algorithms. The efficiency-corrected normalized relative quantity values were used to compare gene expressions among study groups. The PBMC expression of miR-146b and TNFA was downregulated in ESCC patients as compared to healthy subjects. While the level of TLR4 was not different among the study groups, the PBMC level of IL10 was upregulated in ESCC patients. Logistic regression analyses coupled with the ROC curve and cross-validation analysis suggested that PBMC expression may serve as potential candidate biomarker for discriminating ESCC patients from healthy subjects. The present findings, in line with our previous report, propose a particular gene expression pattern in PBMCs of ESCC patients, providing evidence in support of an immune downregulatory mechanism.
Publisher: PeerJ
Date: 16-12-2020
DOI: 10.7717/PEERJ.10377
Abstract: Glycogen synthase kinase-3 (GSK-3β) is a serine/threonine kinase with multifunctions in various physiological procedures. Aberrant level of GSK-3β in kidney cells has a harmful role in podocyte injury. In this article, the expression levels of GSK-3β and one of its upstream regulators, miR-135a-5p, were measured in peripheral blood mononuclear cells (PBMCs) of cases with the most common types of nephrotic syndrome (NS) focal segmental glomerulosclerosis (FSGS) and membranous glomerulonephritis (MGN). In so doing, fifty-two cases along with twenty-four healthy controls were included based on the strict criteria. Levels of GSK-3β mRNA and miR-135 were measured with quantitative real-time PCR. There were statistically significant increases in GSK-3β expression level in NS ( P = 0.001), MGN ( P = 0.002), and FSGS ( P = 0.015) groups compared to the control group. Dysregulated levels of miR-135a-5p in PBMCs was not significant between the studied groups. Moreover, a significant decrease was observed in the expression level of miR-135a-5p in the plasma of patients with NS ( P = 0.020), MGN ( P = 0.040), and FSGS ( P = 0.046) compared to the control group. ROC curve analysis approved a diagnostic power of GSK-3β in discriminating patients from healthy controls (AUC: 0.72, P = 0.002) with high sensitivity and specificity. Dysregulated levels of GSK-3β and its regulator miR-135a may participate in the pathogenesis of NS with different etiology. Therefore, more research is needed for understanding the relationship between them.
Publisher: Research Square Platform LLC
Date: 29-05-2020
DOI: 10.21203/RS.3.RS-28926/V1
Abstract: Background Breast cancer (BC) is the most common invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered a critical nutrition for tumor cell growth and therefore, targeting glutamine metabolism, especially Glutaminase, which catalyzed the conversion of glutamine to glutamate can be beneficial to design anti-cancer agents. Recently, evidence has shown that miRNAs with short length and single strand properties play a significant role in regulating the genes related to glutamine metabolism and may control the development of cancer. Methods Since, in-silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism, the expression level of these two miRNAs was evaluated in eighty BC tissues and margin tissues. The data were analyzed to evaluate the correlation between expression level of these miRNAs and patient’s characteristics such as abortion history, family history, and age. Furthermore, in-silico analysis was applied to predict the potential biological processes and molecular pathways of miR-513c and miR-3163 based on its gene targets. Results In-silico studies revealed the top categories of biological processes and pathways that play a critical role in cancer development were target genes for miR-513c and miR-3163. The current study showed that miR-513c (P-value = 0.02062 and fold change= -2.3801) and miR-3163 (P-value = 0.02034 and fold change= -2.3792) were downregulated in tumor tissues compared to margin tissues. Furthermore, the subgroup studies did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history cancer, and abortion. Conclusion Based on our data, miR-513c and miR-3163 may be offered as a potential diagnosis and therapeutic targets for patients with BC.
Publisher: MDPI AG
Date: 14-10-2019
DOI: 10.3390/IJMS20205088
Abstract: Breast (BCa) and gynecological (GCa) cancers constitute a group of female neoplasms that has a worldwide significant contribution to cancer morbidity and mortality. Evidence suggests that polymorphisms influencing miRNA function can provide useful information towards predicting the risk of female neoplasms. Inconsistent findings in the literature should be detected and resolved to facilitate the genetic screening of miRNA polymorphisms, even during childhood or adolescence, and their use as predictors of future malignancies. This study represents a comprehensive systematic review and meta-analysis of the association between miRNA polymorphisms and the risk of female neoplasms. Meta-analysis was performed by pooling odds-ratios (ORs) and generalized ORs while using a random-effects model for 15 miRNA polymorphisms. The results suggest that miR-146a rs2910164 is implicated in the susceptibility to GCa. Moreover, miR-196a2 rs11614913-T had a moderate protective effect against female neoplasms, especially GCa, in Asians but not in Caucasians. MiR-27a rs895819-G might pose a protective effect against BCa among Caucasians. MiR-499 rs3746444-C may slightly increase the risk of female neoplasms, especially BCa. MiR-124 rs531564-G may be associated with a lower risk of female neoplasms. The current evidences do not support the association of the remaining polymorphisms and the risk of female neoplasms.
Publisher: Hindawi Limited
Date: 21-05-2018
DOI: 10.1111/TBJ.13067
Abstract: Long noncoding RNAs (lncRNAs) constitute a major class of the human transcriptome which play crucial roles in the key biological processes of both normal and malignant breast cells. Although the aberrant expression of lncRNAs has been well-documented in breast cancer (BC), little is currently known about the association between their expression levels in the breast tissue of healthy women and BC risk factors, especially the reproductive or demographic characteristics that are among the most well-known BC risk modifiers. This study was an attempt to investigate the correlation between the expression levels of 2 breast cancer-related lncRNAs, including GAS5 and LSINCT5, and reproductive and demographic characteristics in 145 normal breast tissues that were obtained from women without breast cancer undergoing cosmetic surgery. Total RNA was extracted from fresh normal breast tissues, and the expression level of target lncRNAs was quantified using real-time qPCR. Differences in the mean normalized gene expression among the subgroups of different variables were analyzed. The expression levels of both genes was lower in the overweight-obese (BMI ≥ 25) subgroup than that in the normal BMI (BMI 13 years) than that with early menarche (≤13 years P = .017). These findings may assist to obtain insights into the molecular mechanisms through which the reproductive or obesity-related estrogen changes contribute to the breast carcinogenesis. In conclusion, this study presents the first evidence for the presence of a link between the lncRNA expression and the reproductive or obesity related factors in the breast tissue of healthy women.
Publisher: DoNotEdit
Date: 05-07-2014
DOI: 10.5812/IRCMJ.16659
Publisher: Elsevier BV
Date: 10-2019
DOI: 10.1016/J.MICPATH.2019.103646
Abstract: Escherichia coli is a gram-negative bacterium and it causes a variety of diseases in humans. It causes a wide range of clinical infections in humans urinary tract infections is the most prevalent infection caused by uropathogenic Escherichia coli. In recent years, the observation of antibiotic-resistant genes such as resistance to colistin, makes the Escherichia coli resistant to antibiotics like colistin (polymyxin E), because of that the use of new therapies like peptide nucleic acid (PNA) has attracted the consideration of scientists. The aim of this study is the assessment of the inhibitory role of PNA against mcr-1 gene and reduction of mcr-1 gene expression and MIC in colistin resistant E. coli by PNA. NCBI database was used to design PNA. Our study was carried out on E. coli KP81 bacteria containing the mcr-1 gene. Microbroth dilution (MIC) method was used to survey phenotypic sensitivity and determine the sensitivity of the bacteria to the colistin antibiotic. E. coli KP81 isolates were further investigated by polymerase chain reaction to assess the presence of mcr-1 genes and target genes were quantified by real-time PCR assay using specific primers. The MIC result after treatment with specific PNA showed that the resistance to colistin reduced about three fold and the resistance level dropped from 32 μg/ml to 4 μg/ml. The expression analysis of mcr-1 gene in E. coli KP81 isolate indicates the PNA, 95% reduced the expression of the mcr-1 gene. Our observations showed that by inhibiting the expression of mcr-1, sensitivity to colistin can be defeated. Using higher concentrations of PNA and an in vivo study can reveal more clinical application of this method.
Publisher: Springer Science and Business Media LLC
Date: 12-08-2016
DOI: 10.1007/S12013-016-0754-5
Abstract: Esophageal cancer is the eighth most common cancer worldwide. Also middle-aged obese adults with higher body mass index during childhood have a greater risk to develop esophageal cancer. The contribution of microRNAs to esophageal cancer has been extensively studied and it became clear that these noncoding RNAs may play crucial roles in pathogenesis, diagnosis and prognosis of the disease. Increasing evidences have suggested that polymorphisms perturbing microRNA targetome (i.e., the compendium of all microRNA target sites) are associated with cancers including esophageal cancer. However, the extent to which such variants contribute to esophageal cancer is still unclear. In this study, we applied an in silico approach to systematically identify polymorphisms perturbing microRNA targetome in esophageal cancer and performed various analyses to predict the functional consequences of the occurrence of these variants. The computational results were integrated to provide a prioritized list of the most potentially disrupting esophageal cancer-implicated microRNA targetome polymorphisms along with the in silico insight into the mechanisms with which such variations may modulate microRNA-mediated regulation. The results of this study will be valuable for future functional experiments aimed at dissecting the roles of microRNA targetome polymorphisms in the onset and progression of esophageal cancer.
Publisher: Wiley
Date: 18-07-2019
DOI: 10.1002/JCB.29286
Abstract: Coronary artery disease (CAD) is a multicellular disease characterized by chronic inflammation. Peripheral blood‐mononuclear cells (PBMCs), as a critical component of immune system, actively cross‐talk with pathophysiological conditions induced by endothelial cell injury, reflecting in perturbed PBMC expression. STAT1 is believed to be relevant to CAD pathogenesis through regulating key inflammatory processes and modulating STAT1 expression play key roles in fine‐tuning CAD‐related inflammatory processes . This study evaluated PBMC expressions of STAT1 , and its regulators (miR‐150 and miR‐223) in a cohort including 72 patients with CAD with significant ( ≥ 50%) stenosis, 30 patients with insignificant ( 50%) coronary stenosis (ICAD), and 74 healthy controls, and assessed potential of PBMC expressions to discriminate between patients and controls. We designed quantitative real‐time polymerase chain reaction (RT‐qPCR) assays and identified stable reference genes for normalizing PBMC quantities of miR‐150, miR‐223, and STAT1 applying geNorm algorithm to six small RNAs and five mRNAs. There was no significant difference between CAD and ICAD patients regarding STAT1 expression. However, both groups of patients had higher levels of STAT1 than healthy controls. miR‐150 and miR‐223 were differently expressed across three groups of subjects and were downregulated in patients compared with healthy controls, with the lowest expression levels being observed in patients with ICAD. ROC curves suggested that PBMC expressions may separate between different groups of study subjects. PBMC expressions also discriminated different clinical manifestations of CAD from ICADs or healthy controls. In conclusion, the present study reported PBMC dysregulations of STAT1 , miR‐150, and miR‐223, in patients with significant or insignificant coronary stenosis and suggested that these changes may have diagnostic implications.
Publisher: Wiley
Date: 18-10-2020
DOI: 10.1002/CAM4.3546
Publisher: Wiley
Date: 15-10-2018
DOI: 10.1002/JCB.27860
Abstract: Chronic allograft dysfunction (CAD), the foremost cause of renal graft loss worldwide, is a serious challenge for most of the recipients. As the epigenetic era is emerging, epigenetic biomarkers especially microRNAs (miRNAs) may reflect the current stage of the disease and patient’s therapy response. The current study investigated the potential significance of circulating miRNA‐148a in predicting the renal graft function. Circulating miRNAs were isolated from 53 plasma s les of recipients with histologically validated interstitial fibrosis and tubular atrophy (IFTA, n = 26), and recipients with stable graft function (SGF, n = 27), and also healthy in iduals ( n = 15). The level of miRNA‐148a was evaluated by the quantitative polymerase chain reaction (qPCR) and correlated with clinical and histological parameters. Significantly, miRNA‐148a decreased in IFTA compared with SGF subjects ( P 0.001). MiRNA‐148a levels indicated a significant association with serum creatinine levels ( r = 0.451, P = 0.021) and glomerular filtration rate ( r = −0.520, P = 0.006). MiRNA‐148a expression levels could discriminate IFTA cases from SGF in iduals with an area under the curve of 0.89 ( P 0.001), 97% sensitivity, and 72% specificity. A number of predicted targets that might be involved in CAD by miRNA‐148a were predicted. Plasma cell‐free miRNA‐148a correlated with renal function and histological grades therefore, it may be further investigated as a novel noninvasive molecular marker of the progression to IFTA in renal transplant recipients moreover, the emerging biomarker may become a therapeutic target in the future clinic.
Publisher: Wiley
Date: 04-04-2022
DOI: 10.1002/CAM4.4713
Abstract: Colorectal cancer (CRC) is one of the most common obesity‐associated cancers. Inflammation is also considered the most important factor between obesity and CRC. This study aimed to examine miRNAs binding sites variants on inflammatory genes identified using bioinformatics and systematic approach on clinical s les that were collected from CRC patients and controls. The candidate variants related to CRC inflammatory genes were obtained from genome‐wide association studies and their population‐specific haplotypes. The variants were analyzed according to their genomic position on the miRNA targetome. Targetome variants in inflammation‐related genes were selected for genetic association study by TaqMan genotyping assay. The GG genotype of rs7473 decreased the risk of obesity ( p 0.05). Heterozygous genotype (GA) of rs1547715 decreased the risk of CRC ( p 0.05). In the rs7473/rs1547715 genotype and haplotype, the frequencies of AA/GA and GG/AA lessened in CRC and obesity, respectively ( p 0.05). The variants of rs7473 and rs1547715 were associated with obesity and CRC, respectively. The above‐mentioned associations could be made based on the interactions of these variants with miRNAs.
Publisher: Wiley
Date: 14-11-2019
DOI: 10.1002/JCP.29396
Abstract: Breast cancer is one of the most lethal malignancies in women in the world. Various factors are involved in the development and promotion of the malignancy most of them involve changes in the expression of certain genes, such as microRNAs (miRNAs). MiRNAs can regulate signaling pathways negatively or positively, thereby affecting tumorigenesis and various aspects of cancer progression, particularly breast cancer. Besides, accumulating data demonstrated that miRNAs are a novel tool for prognosis and diagnosis of breast cancer patients. Herein, we will review the roles of these RNA molecules in several important signaling pathways, such as transforming growth factor, Wnt, Notch, nuclear factor-κ B, phosphoinositide-3-kinase/Akt, and extracellular-signal-regulated kinase/mitogen activated protein kinase signaling pathways in breast cancer.
Publisher: Wiley
Date: 17-11-2021
DOI: 10.1111/JCMM.17066
Abstract: The aggressive and highly metastatic nature of triple‐negative breast cancer (TNBC) causes patients to suffer from the poor outcome. HIF‐1 signalling pathway is a prominent pathway that contributes to angiogenesis and metastasis progression in tumours. On the contrary, the undeniable importance of circular RNAs (circRNAs) as multifunctional non‐coding RNAs (ncRNAs) has been identified in breast cancer. These ncRNAs owing to their high stability and specificity have been becoming a hotspot in cancer researches. circRNAs act as competing endogenous RNAs (ceRNAs) and compete with mRNAs for shared miRNAs, thus modulate gene expression. Since the most dysregulated biological functions in TNBC are associated with cellular invasion, understanding the molecular pathogenesis of these processes is a crucial step towards the development of new treatment approaches. The purpose of this study is to undermine the circRNA‐associated ceRNA network involved in HIF‐1 signalling in TNBC using an integrative bioinformatics approach. In the next step, the novel circ_0047303‐mediated ceRNA regulatory axes have been extracted and validated across TNBC s les. We show that circ_0047303 has the highest degree in the circRNA‐associated ceRNA network and shows a significant up‐expression in TNBC. Moreover, our results suggest that circ_0047303 could mediate the upregulation of key angiogenesis‐related genes, including HIF ‐ 1 , EIF4E2 and VEGFA in TNBC through sponging the tumour‐suppressive miRNAs. The circ_0047303 could be a promising molecular biomarker and/or therapeutic target for TNBC.
Publisher: Elsevier BV
Date: 2021
Publisher: Elsevier BV
Date: 12-2015
DOI: 10.1016/J.YGENO.2015.10.004
Abstract: The contribution of microRNAs (miRNAs) to cancer has been extensively investigated and it became obvious that a strict regulation of miRNA-mRNA regulatory network is crucial for safeguarding cell health. Apart from the direct impact of miRNA dysregulation in cancer pathogenesis, genetic variations in miRNAs are likely to disrupt miRNA-target interaction. Indeed, many evidences suggested that SNPs within miRNA regulome are associated with the development of different hematological malignancies. However, a full catalog of SNPs within miRNAs target sites of genes relevant to hematopoiesis and hematological malignancies is still lacking. Accordingly, we aimed to systematically identify and characterize such SNPs and provide a prioritized list of most potentially disrupting SNPs. Although in the present study we did not address the functional significance of these potential disturbing variants, we believe that our compiled results will be valuable for researchers interested in determining the role of target-SNPs in the development of hematological malignancies.
Publisher: Wiley
Date: 21-10-2021
DOI: 10.1002/CBIN.11711
Abstract: Podocytes, highly specified kidney epithelial cells, live under several pathological stimuli and stresses during which they adapt themselves to keep homeostasis. Nevertheless, under extreme stress, a complex scenario of podocyte damage and its consequences occur. Podocyte damage causes foot process effacement and their detachment from the glomerular basement membrane, leading to proteinuria. Podocyte‐derived extracellular vesicles (pEVs), mainly microparticles and exosomes are considered as signaling mediators of intercellular communication. Recently, it has been shown that throughout the injury‐related migration procedure, podocytes are capable of releasing the injury‐related migrasomes. Evidence indicates that at the early stages of glomerular disorders, increased levels of pEVs are observed in urine. At the early stage of nephropathy, pEVs especially migrasomes seem to be more sensitive and reliable indicators of podocyte stress and/or damage than proteinuria. This review highlights the current knowledge of pEVs and their values for the diagnosis of different kidney diseases.
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.AMJMS.2022.05.025
Abstract: Glomerular injury is the major cause of chronic kidney diseases (CKD) worldwide and is characterized by proteinuria. Glomerulonephritis (GN) has a wide spectrum of etiologies, the intensity of glomerular damage, histopathology, and clinical outcomes that can be associated with the landscape of the nephritogenic immune response. Beyond impaired immune responses and genetic factors, recent evidence indicates that microbiota can be contributed to the pathogenesis of GN and patients' outcomes by impacting many aspects of the innate and adaptive immune systems. It is still unknown whether dysbiosis induces GN or it is a secondary effect of the disease. Several factors such as drugs and nutritional problems can lead to dysbiosis in GN patients. It has been postulated that gut dysbiosis activates immune responses, promotes a state of systemic inflammation, and produces uremic toxins contributing to kidney tissue inflammation, apoptosis, and subsequent proteinuric nephropathy. In this review, the impact of gastrointestinal tract (GI) microbiota on the pathogenesis of the primary GN will be highlighted. The application of therapeutic interventions based on the manipulation of gut microbiota with special diets and probiotic supplementation can be effective in GN.
Publisher: Wiley
Date: 28-02-2019
DOI: 10.1002/JCB.28505
Abstract: Emerging evidence indicates that some altered patterns of methylation that occur in breast tumors may also be found in breast tissue of healthy women in relation to the breast cancer (BC) risk factors. Progesterone receptor (PR) isoform α is a crucial regulator of breast hormone responsiveness and its hypermethylation plays an important role in the initiation and development of breast tumors. However, such a methylation change in healthy women and its link with the different risk factors has not yet been investigated. In the present study, we aimed to examine the relationship of possible methylation changes within a critical region in the promoter CpG island of PGR‐α (progesterone receptor α) gene in the healthy women with a set of reproductive and nonreproductive BC risk factors. The breast tissues were collected from 120 cancer‐free women who had undergone cosmetic mammoplasty. The genomic DNA was extracted from the breast tissues and the methylation level of PGR‐α promoter CpG island was determined by using MeDIP‐qPCR assay. Using regression analysis, we found that increasing menarche age is inversely associated with the high methylation of PGR‐α promoter ( β = −0.790, SE = 0.362 P = 0.031). Although lactating women had more methylation than nonlactating women ( P = 0.026, the t test), this result was not confirmed by regression models. Such an observation may be helpful in better understanding of the underlying mechanisms by which early age at menarche increases the risk of BC. However, this perspective requires further validations in larger studies of more subjects as well as the inclusion of other related genes.
Publisher: Mary Ann Liebert Inc
Date: 06-2017
Abstract: Iran is located in the Asian esophageal cancer belt. It is a high-risk region for esophageal squamous cell carcinoma (ESCC). The extent to which genetic components, especially variants within miRNAs or their binding sites, contribute to risk of ESCC in the region is not yet fully understood. Herein, tests were done on an Iranian cohort to evaluate the association of miRNA-related polymorphisms in miR-423 (rs6505162) and peroxisomal biogenesis factor 6 (PEX6) (rs1129186 within a miR-149-5p-binding site) with the risk of ESCC risk. This study recruited 200 ESCC patients and 300 healthy in iduals. Genotyping was performed using the polymerase chain reaction-restriction fragment length polymorphism method. Target genes and biological processes that are regulated by miR-423 and may be affected by a change in miR-423 expression were identified by in silico analysis. Logistic regression analyses revealed an association between rs6505162 and ESCC, assuming codominant (AA vs. CC, odds ratios, OR [95% confidence interval, CI]: 0.32 [0.15-0.69], p-value: 0.0076), recessive (AA vs. CC+CA, OR [95% CI]: 0.35 [0.16-0.73], p-value: 0.0027), and log-additive models (OR [95% CI]: 0.69 [0.52-0.91], p-value: 0.0084). No significant association was observed for PEX6 rs1129186. In silico analyses revealed several genes and biological processes that are regulated by miR-423 in ESCC. This study identified the first evidence of an association of a miRNA-related variant with risk of ESCC in an Iranian cohort. PEX6 rs1129186 may not modulate the risk of ESCC in the cohort.
Publisher: Bentham Science Publishers Ltd.
Date: 05-2021
DOI: 10.2174/1871520620666200924105352
Abstract: Breast Cancer (BC) is the most common malignancy among women with a high mortality rate. The blockade of asparagine-related pathways may be an effective measure to control the progression and reduction of BC metastasis potential. Recently, it has been shown that various miRNAs, as part of small non-coding RNAs, have a great role in cancer development, especially asparagine-related pathways, to modulate the invasiveness. This study aimed to evaluate the expression of miR-130a-5p and miR-615-3p in tumoral and nontumoral adjacent tissues of patients with BC. There is a chance that asparagine metabolism is influenced by miR-130a-5p and miR-615-3p as confirmed by bioinformatics analysis. Hence, real-time PCR was conducted on eighty BC tumoral and non-tumoral adjacent tissues to evaluate the expression level of the two miRNAs. To predict the potential biological process and molecular pathways of miR-130a-5p, an in silico analysis was performed. This study indicated that miR-130a was downregulated in tumoral tissues compared to non-tumoral adjacent tissues (P-value= 0.01443 and fold change= -2.5137), while miR-615-3p did not show a significant difference between the two groups. Furthermore, the subgroup studies did not reveal any significant correlation between the expression of these two miRNAs and subfactors. Furthermore, in silico studies unraveled several biological processes related to amino-acid metabolism, as well as pathways related to tumor development such as Phosphatase and Tensin Homolog (PTEN) and JAK-STAT pathways among miR-130a-5p target genes. Our findings indicate that miRNA-130a-5p is downregulated in BC tissues and may play a tumor suppressor role in patients with BC. Therefore, it may be suggested as a potential diagnostic and therapeutic target for BC.
Publisher: Springer Science and Business Media LLC
Date: 28-01-2016
DOI: 10.1007/S10528-016-9713-5
Abstract: The present work is aimed at finding variants associated with Type 1 and Type 2 diabetes mellitus (DM) that reside in functionally validated miRNAs binding sites and that can have a functional role in determining diabetes and related pathologies. Using bioinformatics analyses we obtained a database of validated polymorphic miRNA binding sites which has been intersected with genes related to DM or to variants associated and/or in linkage disequilibrium (LD) with it and is reported in genome-wide association studies (GWAS). The workflow we followed allowed us to find variants associated with DM that also reside in functional miRNA binding sites. These data have been demonstrated to have a functional role by impairing the functions of genes implicated in biological processes linked to DM. In conclusion, our work emphasized the importance of SNPs located in miRNA binding sites. The results discussed in this work may constitute the basis of further works aimed at finding functional candidates and variants affecting protein structure and function, transcription factor binding sites, and non-coding epigenetic variants, contributing to widen the knowledge about the pathogenesis of this important disease.
Publisher: Frontiers Media SA
Date: 15-03-2019
Publisher: Mary Ann Liebert Inc
Date: 05-2016
Abstract: Recent studies have suggested that single-nucleotide polymorphisms (SNPs) in miRNA genes or their binding sites may alter an in idual's susceptibility to coronary artery disease (CAD). In the present study, the association between two such SNPs (rs2910164 in miR-146a and rs12190287, which disrupts miRNA binding to TCF21) and CAD, in an Iranian population, was evaluated and in silico analyses were conducted to predict disease-related effects of miR-146a rs2910164. The study population consisted of angiographically confirmed CAD patients (n = 300) and asymptomatic controls (n = 300). Genotyping was performed using the TaqMan genotyping assay. A multivariate regression analysis revealed that rs2910164 was associated with an increased CAD risk in the dominant model. In comparison to GG homozygotes, in iduals who carry at least one C allele had a significantly higher risk of CAD (GC+CC vs. GG, odds ratios [OR]: 1.82, 95% confidence intervals [CI]: 1.18-2.80, p = 6.358e-3). Similarly, TCF21 rs12190287 was observed to be associated with CAD in a log-additive model (OR: 0.63, 95% CI: 0.45-0.88, p = 6.584e-3). An in silico analysis revealed that rs2910164 may modify the miR-146a-3p-mediated regulation of several biological processes that are implicated in CAD, like those that are related to the regulation of apoptosis and immune response. Our data provide the first evidence for the association of miR-146a rs2910164 and TCF21 rs12190287 with CAD in an Iranian population, encouraging further research to elucidate the disease-related effects of miR-146a rs2910164.
Publisher: Informa UK Limited
Date: 04-2019
DOI: 10.2147/IJN.S194596
Publisher: Mary Ann Liebert Inc
Date: 08-2017
Abstract: Reproductive history and obesity are among the well-recognized risk factors in the development of breast cancer, which are partially mediated by the increased exposure of breast tissues to estrogens. However, only a few studies have investigated the link between these risk factors and the pattern of methylation signatures in the breast tissue of healthy women. The role of the estrogen receptor 1 (ESR1) gene hypermethylation is reportedly important in the development of breast cancer. Thus, it is speculated that such ESR1 epigenetic changes may be influenced or shaped by obesity and reproductive history-related factors before and during breast carcinogenesis. Breast s les were collected from 120 cancer-free women who had undergone cosmetic mammoplasty. DNA was extracted from the breast tissues and, then, the methylation levels at the promoter and exon 1 regions of the ESR1 gene CpG island were determined by using the methylated DNA immunoprecipitation-quantitative PCR assay. The methylation level of the ESR1 promoter observed in women with a body mass index (BMI) ≥30 kg/m These findings provide new hints about the relationship between epigenetic changes within the ESR1 gene CpG island and postmenopausal obesity and aging in cancer-free women. In terms of lifestyle intervention opportunities, this study also highlights the significance and feasibility of such interventions for BMI as a modifiable risk factor.
Publisher: Research Square Platform LLC
Date: 20-04-2022
DOI: 10.21203/RS.3.RS-1566888/V1
Abstract: Glioblastoma is one of the most frequently occurring and malignant brain tumors. Due to the importance of microRNAs and HIF1α gene that is involved in the angiogenesis and growth of tumor cells, this study aimed to evaluate the correlation of the expression of HIF1α gene with miR-148a, miR-31, and miR-221, which were reported by in silico analysis as risky microRNAs in GBM. The findings obtained from Real-Time PCR using TaqMan Assay indicated the significant difference in the expression of HIF1α gene and microRNAs between the patient and healthy groups and the expression changes were obtained point to point in the patients so they can be considered as important biomarkers in glioblastoma. The obtained AUC from the ROC analysis indicated that the analysis of the expression of HIF1α and miR-148a, miR-31 & miR-221 genes can be used to distinguish healthy and patient groups nevertheless, the correlation of HIF1α gene expression with the microRNAs was reported low according to Pearson’s correlation coefficient. Thus the significant increase in HIF1α gene expression is probably controlled by other molecules. By using bioinformatics analysis Gene Ontology biological process MSigDB Hallmark and KEGG pathway enrichment analysis of PPI network was carried out with Enrichr web-based application. The axon guidance pathway, proteoglycan in cancer and some of intracellular signaling pathways identified as the most important signaling pathways. The results of MSigDB_Hallmark pathway enrichment analysis introduced hypoxia signaling pathway with less involvement from these micoRNAs. Therefore these microRNAs can be considered in Glioblastoma cell infiltration through the myelinated nerve fibers of white matter tracts.
Publisher: Informa UK Limited
Date: 06-08-2020
Publisher: Wiley
Date: 08-10-2020
DOI: 10.1002/BIOF.1680
Abstract: Steroid‐resistant nephrotic syndrome (SRNS) is a clinical challenge with variable clinical outcomes. In patients with SRNS, unsuccessful anti‐inflammatory and anti‐proteinuric effects of steroids lead to end‐stage renal disease (ESRD). Our objective was to define the expression pattern of the glucocorticoid receptors (GR) α and β and their epigenetic regulators (miR‐24, miR‐30a, and miR‐370) in a group of adults with SRNS. In this regard, sixty primary NS patients with focal segmental glomerulosclerosis (FSGS, N = 30) and membranous glomerulonephritis (MGN, N = 30) and also healthy volunteers ( N = 24) were enrolled. Real‐time PCR was performed to evaluate the expression levels of the aforementioned genes in peripheral blood mononuclear cell (PBMC) s les. Furthermore, an in‐silico analysis was performed to understand the signaling pathways and biological procedures that may be targeted by these microRNAs in NS. The decreased and increased levels of GRα and GRβ were not significant, respectively. Statistically significant reduced miR‐24 levels were observed between control/MGN ( p = .022) and MGN/FSGS ( p = .032) groups. Additionally, a decrease was detected in miR‐30a between MGN and FSGS ( p = .049) groups. There was a significant increase in miR‐370 expression level between control and NS groups ( p = .029), as well as control/MGN ( p = .008), and MGN/FSGS ( p = .046). Bioinformatics analysis predicted the possible targets of the studied genes including genes involved in TGF‐β, Notch1, and p53 signaling pathways, regulation of gene expression, intracellular signal transduction, negative regulation of response to the stimulus, cell‐cell signaling, and cell activation in the pathogenesis of SRNS. Taken all together, dysregulated levels of GRα, GRβ were not attributed to SRNS in our patients. It seems that pharmacokinetics and the genetic variations in podocyte‐related genes may be associated with the steroid‐resistance in our adult patients with NS rather than GR expression.
Publisher: Wiley
Date: 11-12-2018
DOI: 10.1002/JCB.28269
Abstract: Recently, it has been revealed that estrogen‐related reproductive factors are linked with some early gene expression lesions associated with malignancy in clinically healthy breasts. Accordingly, the aim of the current study was to evaluate the association of expression levels of estrogen‐related long noncoding RNAs (lncRNAs) upstream Eleanor (u‐Eleanor) and HOX antisense intergenic RNA (HOTAIR) with the different patterns of reproductive factors in breast tissue of healthy women. The subjects of this study were 98 cancer‐free women who had undergone cosmetic mammoplasty. The expression levels of u‐Eleanor and HOTAIR were measured using quantitative real‐time polymerase chain reaction. The results of the current study showed that the women without a history of breastfeeding had a high‐level expression of u‐Eleanor compared with the women with a breastfeeding duration greater than 6 to 24 months ( P = 0.03) as well as the women with a breastfeeding duration of more than 24 months ( P = 0.005). Furthermore, a higher expression of u‐Eleanor was found in the women with a short breastfeeding duration for 1 to 6 months than that in the women with a breastfeeding duration of greater than 24 months ( P = 0.02). In the same way, the results of correlation test ( r = −0.258 P = 0.036) and multivariate regression model ( β = −0.321 P = 0.023) are indicative of a significant relationship of elevated expression of u‐Eleanor with decreasing breastfeeding duration in the women. These findings could be important to identify the molecular mechanisms behind the relationship between a lack or short duration of the breastfeeding and the risk of breast cancer, which has previously been reported by epidemiological studies.
Publisher: Wiley
Date: 21-10-2019
DOI: 10.1002/CAM4.2600
Publisher: Springer Science and Business Media LLC
Date: 04-01-2018
DOI: 10.1038/S41380-017-0012-2
Abstract: Autosomal recessive (AR) gene defects are the leading genetic cause of intellectual disability (ID) in countries with frequent parental consanguinity, which account for about 1/7th of the world population. Yet, compared to autosomal dominant de novo mutations, which are the predominant cause of ID in Western countries, the identification of AR-ID genes has lagged behind. Here, we report on whole exome and whole genome sequencing in 404 consanguineous predominantly Iranian families with two or more affected offspring. In 219 of these, we found likely causative variants, involving 77 known and 77 novel AR-ID (candidate) genes, 21 X-linked genes, as well as 9 genes previously implicated in diseases other than ID. This study, the largest of its kind published to date, illustrates that high-throughput DNA sequencing in consanguineous families is a superior strategy for elucidating the thousands of hitherto unknown gene defects underlying AR-ID, and it sheds light on their prevalence.
Publisher: Wiley
Date: 17-01-2020
DOI: 10.1002/JCP.29442
Abstract: Breast cancer is a major clinical challenge that affects a wide range of the female population and heavily burdens the health system. In the past few decades, attempts have been made to understand the etiology of breast cancer, possible environmental risk factors, and the genetic predispositions, pathogenesis, and molecular aberrations involved in the process. Studies have shown that breast cancer is a heterogeneous entity each subtype has its specific set of aberrations in different cell signaling pathways, such as Notch, Wnt/β-catenin, transforming growth factor-β, and mitogen-activated protein kinase pathways. One novel group of molecules that have been shown to be inducted in the regulation of multiple cell signaling pathways is the long noncoding RNAs (lncRNAs). These molecules have important implications in the regulation of multiple signaling pathways by interacting with various genes, affecting the transcription process, and finally, playing roles in posttranslational control of these genes. There is growing evidence that lncRNAs are involved in the process of breast cancer formation by effecting the aforementioned signaling pathways, and that this involvement can have significant diagnostic and prognostic values in clinical contexts. The present review aims to elicit the significance of lncRNAs in the regulation of cell signaling pathways, and the resulting changes in cell survival, proliferation, and invasion, which are the hallmarks of breast cancer.
Publisher: Springer Science and Business Media LLC
Date: 16-06-2021
DOI: 10.1186/S13104-021-05647-Z
Abstract: Breast cancer (BC) is the most significant and lethal type of cancer in women. Although there are many newly develop chemotherapy drugs for patients with BC treating at various stages, drug resistance is the most important obstacle in their effectiveness for BC treatment. On the other hand, microRNAs are considered key regulators of genes involved in carcinogenesis and chemoresistance in cancers. The purpose of this study was to evaluate the role of miR-152-3p and miR-185 in intrinsic chemoresistance and proliferation of BC. In addition, the potential role of these miRNAs during chemoresistance was evaluated through possible signaling pathways. Here, miR-152-3p was significantly downregulated in tumor tissues compared to the corresponding margin tissues in patients with BC ( p -value ≥ 0.04407 and fold change = − 2.0552). In contrast, no statistically significant difference was observed in the miR-185 expression between the two groups. Furthermore, no significant correlation was found between the expression of these two miRNAs and subfactors, including cancer family history, abortion, and age. Downregulation of miR-152-3p could be considered a promising regulator of BC chemoresistance.
Publisher: Wiley
Date: 15-06-2018
DOI: 10.1002/JCB.26754
Abstract: Breast cancer (BC) is the leading cause of cancer mortality in women worldwide. It recently was proven that miRNAs play a critical role in BC development. The use of natural agents for control of cancer by modulating miRNAs is promising. Oleuropein is a natural polyphenolic agent with anti‐neoplastic properties and is well tolerated by humans. This study was undertaken to determine the therapeutic effects of oleuropein through modulation of master oncomiRs (miR‐21 and miR‐155) in BC cells. The present study provides the first link between miRNA and oleuropein as a mechanism in BC. MCF‐7 cells were tested with and without oleuropein and the cell viability, apoptosis, and migration were examined. The effect of oleuropein on miR‐21 and miR‐155 expression was assessed through qRT‐PCR. It was found that oleuropein induced apoptosis and retarded cell migration and invasion in a dose‐dependent manner in the human MCF7 BC cell line. It was observed that oleuropein significantly decreased expression of both miR‐21 and miR‐155 over time in a dose‐dependent manner. These results demonstrate that oleuropein is a potential therapeutic and preventive agent for BC. Oleuropein exhibits an anti‐cancer effect by modulation of tumor suppressor gene expression, which is targeted by oncomiRs.
Publisher: Elsevier BV
Date: 02-2021
Publisher: Informa UK Limited
Date: 02-10-2020
DOI: 10.1080/08820139.2020.1828454
Abstract: Esophageal cancer is one of the least studied aggressive tumors, with the squamous cell carcinoma (ESCC) being the most frequent histological type around the world. Growing evidence has shown that the abnormal expression of microRNAs (miRNAs) in peripheral blood mononuclear cells (PBMCs) is closely related to the pathogenesis of cancers. MiR-146a is a crucial regulator of inflammatory cascades. There is currently no data available regarding the possible role of miR-146a in PBMCs of ESCC patients. We evaluated the expression of miR-146a, as well as its target genes (IRAK1 and TRAF6) and its associated immune effectors (NF-κB1, IL1B, and IL6) in PBMCs of 40 ESCC patients and 50 control subjects. The geometric mean expression of five transcripts was used for normalizing expressions. The PBMC level of miR-146a, as measured by RT-qPCR, was upregulated, whereas levels of its target genes, IRAK1 and TRAF6, were downregulated in ESCC patients. NF-κB1 and IL6 was downregulated in PBMCs of ESCC patients. There was no difference in terms of the IL1B level between patients and the control group. Logistic regression and receiver operating characteristic curve analysis suggested that a model with PBMC levels of either NF-κB1+ IL6 or NF-κB1+ miR-146a as predictors may discriminate ESCC patients from subjects of the control group. Our findings, in the context of the current literature, may suggest a possible downregulatory mechanism of immune responses in PBMCs of ESCC patients.
Publisher: Bentham Science Publishers Ltd.
Date: 31-12-2020
DOI: 10.2174/1871520620666200910123428
Abstract: Metabolic reprogramming is a significant property of various cancer cells, which most commonly arises from the Tumor Microenvironment (TME). The events of metabolic pathways include the Warburg effect, shifting in Krebs cycle metabolites, and the rate of oxidative phosphorylation, potentially providing energy and structural requirements for the development and invasiveness of cancer cells. TME and tumor metabolism shifting have a close relationship through bidirectional signaling pathways between stromal and tumor cells. Cancer- Associated Fibroblasts (CAFs), as the most dominant cells of TME, play a crucial role in the aberrant metabolism of cancer. Furthermore, the stated relationship can affect survival, progression, and metastasis in cancer development. Recently, exosomes are considered one of the most prominent factors in cellular communications considering effective content and bidirectional mediatory effect between tumor and stromal cells. In this regard, CAF-Derived Exosomes (CDE) exhibit an efficient obligation to induce metabolic reprogramming for promoting growth and metastasis of cancer cells. The understanding of cancer metabolism, including factors related to TME, could lead to the discovery of a potential biomarker for diagnostic and therapeutic approaches in cancer management. This review focuses on the association between metabolic reprogramming and engaged microenvironmental, factors such as CAFs, and the associated derived exosomes.
Publisher: Future Medicine Ltd
Date: 02-2019
Abstract: MiRNAs have immerged as essential modulators of key cellular procuresses involved in post-transcriptional regulation of the human transcriptome. They are essential components of complex regulatory networks that modulate most important physiological functions of cells. MicroRNA-155 (miR-155) is a multifaceted regulator of cell proliferation, cell cycle, development, immunity and inflammation that plays pivotal, and sometimes contradictory, roles in numerous cancers including esophageal cancer. Here, we review the intricate role of miR-155 in cancer by exemplifying carcinogenesis of various tumors, focusing on recent findings that may provide a link between miR-155 and esophageal cancer-related pathways.
Publisher: Springer Science and Business Media LLC
Date: 21-01-2019
DOI: 10.1007/S12253-019-00579-3
Abstract: One of the highest risk of esophageal squamous cell carcinoma (ESCC) in the world has been reported in Iran, which is located in the Asian esophageal cancer belt. ESCC constitutes 90% of the esophageal cancer cases in Iran. Genome wide association studies (GWASs) in Chinese have identified a number of candidate variants, of which PLCE1rs2274223, C20orf54rs13042395 and RUNX1rs2014300 are studied in high risk populations including Chinese, Caucasians and Africans. However, results are inconsistent and it is unknown whether similar associations exist in Iranian population. We evaluated association of three GWAS identified variants with risk of ESCC in an Iranian cohort consisted of 200 ESCC patients and 300 healthy controls and conducted meta-analysis of ESCC risk associated with rs2274223 (involving 9810 cases and 13,128 controls) and rs13042395 (involving 2363 cases and 5329 controls). Logistic regression analysis showed that rs2274223 was associated with ESCC under codominant [GG/AA, 2.47(1.17-5.23), P:0.021], dominant [AG + GG/AA, 1.57(1.09-2.27), P:0.016], recessive [GG/AA+AG, 2.18(1.04-4.56), P:0.036] and log-additive models [1.51(1.12-2.02), P:0.006]. C20orf54 rs13042395 was not associated with ESCC under any genetic model. RUNX1 rs2014300 was associated with risk of ESCC assuming codominant [AG/GG, 0.63(0.41-0.97), P:0.018], dominant [AG + AA/GG, 0.59 (0.39-0.89), P:0.010] and log-additive models [0.61 (0.42-0.87), P: 0.005]. Meta-analysis found significant associations between rs2274223 and ESCC under all analyzed genetic models. However, meta-analysis stratified by ethnicity showed a significant association in Asians but not non-Asian populations. No significant association was found for rs13042395 in meta-analysis. This study provided first evidence for association of GWAS-identified variants with risk of ESCC in an Iranian cohort.
Publisher: Elsevier BV
Date: 02-2020
DOI: 10.1016/J.MICPATH.2019.103825
Abstract: Multidrug-resistant Acinetobacter baumannii isolates cause critical problems in health-care environments. AdeABC is a resistance-nodulation-cell ision (RND)-type multidrug efflux pump conferring resistance to clinically essential antibiotics in A. baumannii, such as ciprofloxacin. This study aimed to target adeB gene with antisense peptide nucleic acid (PNA) and investigate its effect on resistance to antibiotics. NCBI database was used to design appropriate PNA to target adeB gene, by connecting PNA to mRNA, the translation of mRNA can be prevented. Three clinical isolates and A. baumannii ATCC 17978 were treated with the designed PNA by electroporation and competence procedure. Minimum Inhibitory concentration (MIC) of ciprofloxacin, colistin, and tetracycline were determined by microbroth dilution method. In addition, the expression level of adeB gene was measured by quantitative real-time PCR (qRT-PCR). Isolates used in this study had mutations in gyrA and parC genes corresponding to resistance to ciprofloxacin. MIC of resistance to ciprofloxacin after treatment with PNA was reduced from 32 μg/ml to16 μg/ml in A. baumannii ATCC 17978 isolate. Susceptibility level of tetracycline, in the 2 clinical isolates was decreased from 64 μg/ml to 32 μg/ml and in the other isolate was reduced from 128 μg/ml to 64 μg/ml. The expression level of adeB gene was decreased in A. baumannii ATCC 17978 (P > 0.01) but not in clinical isolate (P = 0.107). Findings of the present study indicate overexpression of adeB efflux pump has extra effect on resistance to antibiotics in isolates with a defined mechanism of resistance. Antisense technology is a feasible technique to suppress the function of these genes, which may be further exploited to control multidrug-resistant isolates.
Publisher: Wiley
Date: 24-05-2018
DOI: 10.1111/IJI.12364
Abstract: HLA-G is a nonclassical Class I major histocompatibility complex (MHC) gene. This gene has a limited protein alteration that is produced by alternative splicing and can be important in the preservation of pregnancy. Recent findings suggest that alteration in HLA-G gene expression can lead to pregnancy failure, such as recurrent pregnancy loss (RPL). As the promoter SNPs of the gene may impact the HLA-G expression levels, the study of these SNPs is very important. In this study, for the promoter region of HLA-G gene in the case group (100 women with a history of two or more repeated miscarriages) and the control group (100 women with at least two successful pregnancies), PCR reaction was performed. Thereafter, PCR products were sequenced and the results were compared between the two groups. The results showed that -1573T>C and -1746C>A SNPs in the promoter of the HLA-G gene associated with RPL. The outcome of the haplotype analysis also showed that the association of two haplotypes, including H1 (ATCCAGGTACGCAA) and H2 (CTTCGAGAACGCAG) with RPL, is significant. The results showed that H1 is associated with a decreased and H2 is associated with an increased risk of RPL. These results indicate the importance of the HLA-G promoter SNPs in the pregnancy outcome. But to reach a more definite conclusion, subsequent studies on 3' UTR and other positions with polymorphism in the 5' UTR regions larger s les are necessary.
Publisher: Hindawi Limited
Date: 20-04-2014
DOI: 10.1111/AND.12274
Abstract: Nuclear receptor subfamily 5 group A member 1 (NR5A1) encodes a nuclear receptor that regulates transcription of multiple genes involved in adrenal and gonadal development, steroidogenesis and the reproductive axis. Human mutations in NR5A1were initially found in two 46, XY female patients suffering from severe gonadal dysgenesis and primary adrenal failure. However, more recent case reports have suggested that heterozygous mutations in NR5A1 may also contribute to the male infertility aetiology. We have analysed the coding sequence of NR5A1 in a cohort of 90 well-characterised idiopathic Iranian azoospermic infertile men versus 112 fertile men. Heterozygous NR5A1 mutations were found in 2 of 90 (2.2%) of cases. These two patients harboured missense mutations within the hinge region (p.P97T) and ligand-binding domain (p.E237K) of the NR5A1 protein. In silico analysis of the mutations showed that founded mutations could be detrimental. In conclusion, findings of the current and previous studies suggest that mutations in the NR5A1 gene are not common in azoospermia, and male infertility and inclusion of NR5A1 mutation screening in the diagnostic workup of male infertility may seem unnecessary.
Publisher: Elsevier BV
Date: 2019
DOI: 10.1016/J.PHRS.2018.11.023
Abstract: Systemic lupus erythematosus (SLE) is a complex, inflammatory, and autoimmune disease triggered by complicated interactions of different factors. A major contributor to morbidity and mortality in SLE is lupus nephritis (LN). To date, the cause of SLE and LN is incompletely understood but a combination of genetic and environmental factors is thought to be involved. In recent years, there have been attempts to consider the intestinal microbial profiles, microbiota, and its role in the pathogenesis of the disease. The composition and elements of gut microbiota have major roles in antibody production, shaping the human B cell repertoire, homeostasis of different populations of helper T cell and Th17:Treg balance, and regulation of the levels of different Th17 cell subpopulations. Disturbance of gut microbiota, called dysbiosis, leads to the development of autoimmunity. To date, few studies have characterized the microbiota composition in SLE. In this review, we will highlight novel findings describing the effect of genetic, epigenetic, and environmental factors on gut microbiota and immune system. Moreover, we will discuss the possible association between SLE and microbiota composition and concerning how its changes may contribute to the onset of SLE and LN. Interest in this area has been grown to consider the microbiome as a potential therapeutic target in future.
Publisher: Research Square Platform LLC
Date: 30-12-2020
DOI: 10.21203/RS.3.RS-136137/V1
Abstract: Background: Breast cancer (BC) is the most common invasive cancer with different subtypes that its metabolism is unique compared with normal cells. Glutamine is considered critical nutrition, that many cancer cells, particularly BC cells are dependent on it for growth and proliferation. Therefore, targeting glutamine metabolism, especially enzymes related to this pathway, can be beneficial to design anti-cancer agents. Recently, evidence has shown that miRNAs with a short length and single-strand properties play a significant role in regulating the genes related to glutamine metabolism and may control the development of cancer. Methods: In-silico analysis confirmed that miR-513c and miR-3163 might be involved in glutamine metabolism, the expression level of these two miRNAs was examined in eighty BC tissues and margin tissues. Furthermore, in-silico analysis was applied to predict the potential biological processes and molecular pathways of miR-513c and miR-3163 based on their gene targets. Results: In-silico studies revealed the top categories of biological processes and cellular pathways that play a critical role in metabolism reprogramming and cancer development were target genes for miR-513c and miR-3163. The current study showed that miR-513c (p-value= 0.02062 and fold change= -2.3801) and miR-3163 (p-value= 0.02034 and fold change= -2.3792) were downregulated in tumor tissues compared to margin tissues. Furthermore, the subgroup analysis did not show any substantial relationship between expression levels of these two miRNAs and factors such as age, family history cancer, and abortion. Conclusion : miR-513c and miR-3163 are downregulated in BC tissues, which may act as tumor suppressors and may also be considered as potential therapeutic target for patients with BC.
Publisher: Elsevier BV
Date: 12-2016
DOI: 10.1016/J.GENE.2016.08.054
Abstract: In recent years, genome-wide association studies (GWAS) have made great progress in elucidating the genetic influence on complex traits. An overwhelming number of GWAS signals resides in regulatory elements, therefore most post-GWAS studies focused only on transcriptional regulatory variants. However, recent findings have expanded the spectrum of trait/disease-associated regulatory variants beyond transcriptional level and highlighted the importance of post-transcriptional variants like those in miRNA targetome. The present work integrated genome-wide association data of coronary artery disease (CAD) with population-specific linkage disequilibrium structures from 1000 Genomes Project to map disease associations to miRNA targetome. Moreover, we performed a variety of functional prediction analyses to prioritize disease-associated variants (DAVs) influencing miRNA targetome and in-silico analyses to get insights into their functional significance. In conclusion, although the role of miRNA targetome variations in the development of CAD still has to be fully elucidated, we provided a systematic bioinformatics approach to the miRNA targetome variations in CAD. The results of this study will be valuable for researchers interested in the identification of CAD GWAS signals that may implicate polymorphic miRNA targeting.
Publisher: Wiley
Date: 18-09-2012
Publisher: Informa UK Limited
Date: 06-01-2020
Location: Iran (Islamic Republic of)
Location: Iran (Islamic Republic of)
Location: Iran (Islamic Republic of)
No related grants have been discovered for Milad Bastami.