ORCID Profile
0000-0003-0818-3481
Current Organisations
Universidad de Málaga
,
Coccosphere Environmental Analysis
,
Queensland University of Technology
,
The Daffodil Centre
,
University of Sydney
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Publisher: Elsevier BV
Date: 12-2015
Publisher: Elsevier BV
Date: 02-2019
DOI: 10.1016/J.CBPC.2018.11.003
Abstract: The present study aimed to identify differentially expressed genes (DEGs) under silver nanoparticle (AgNPs) treatment. We used a meta-analysis approach to integrate four publicly available microarray datasets, containing control and epithelium s les treated by either AgNPs- or Ag ions. The Fisher's method combined p-values of studies. Post hoc analyses including protein-protein interaction (PPI) and the overrepresentation test were conducted. Analytical results identified 1652 DEGs associated with AgNPs exposure. The most significant up-regulated genes, including MT1H, MT1X, and MT2A were metallothionein family members. The most significant down-regulated gene, TM4SF5, is a novel biomarker for AgNPs exposure. The PPI network analysis revealed that a member of the heat shock protein family, HSP90AA1, is the top up-regulated "hub" gene. Up-regulation of heat shock proteins and metallothionein genes is part of a cellular response to oxidative stress induced by AgNPs treatment. Interestingly, AgNPs may interact negatively with blood coagulation and amino acid metabolism systems.
Publisher: Springer Science and Business Media LLC
Date: 23-12-2016
DOI: 10.1007/S13277-015-4553-1
Abstract: Acute lymphoblastic leukemia (ALL) is the major neoplasia type among children. Despite the tremendous success of current treatment strategies, drug resistance still remains a major cause of chemotherapy failure and relapse in pediatric patients. Overwhelming evidence illustrates that microRNAs (miRNAs) act as post-transcriptional regulators of drug-resistance-related genes. The current study was aimed at how dysregulated miRNA-mRNA-signaling pathway interaction networks mediate resistance to four commonly used chemotherapy agents in pediatric ALL, including asparaginase, daunorubicin, prednisolone, and vincristine. Using public expression microarray datasets, a holistic in silico approach was utilized to investigate candidate drug resistance miRNA-mRNA-signaling pathway interaction networks in pediatric ALL. Our systems biology approach nominated significant drug resistance and cross-resistance miRNAs, mRNAs, and cell signaling pathways based on anti-correlative relationship between miRNA and mRNA expression pattern. To sum up, our systemic analysis disclosed either a new potential role of miRNAs, or a possible mechanism of cellular drug resistance, in chemotherapy resistance of pediatric ALL. The current study may shed light on predicting drug response and overcoming drug resistance in childhood ALL for subsequent generations of chemotherapies.
Publisher: Elsevier BV
Date: 12-2015
Publisher: Springer Science and Business Media LLC
Date: 16-06-2022
DOI: 10.1038/S42003-022-03540-4
Abstract: Aberrant DNA methylation has emerged as a hallmark in several cancers and contributes to risk, oncogenesis, progression, and prognosis. In this study, we performed imputation-based and conventional methylome-wide association analyses for breast cancer (BrCa) and prostate cancer (PrCa). The imputation-based approach identified DNA methylation at cytosine-phosphate-guanine sites (CpGs) associated with BrCa and PrCa risk utilising genome-wide association summary statistics ( N BrCa = 228,951, N PrCa = 140,254) and prebuilt methylation prediction models, while the conventional approach identified CpG associations utilising TCGA and GEO experimental methylation data ( N BrCa = 621, N PrCa = 241). Enrichment analysis of the association results implicated 77 and 81 genetically influenced CpGs for BrCa and PrCa, respectively. Furthermore, analysis of differential gene expression around these CpGs suggests a genome-epigenome-transcriptome mechanistic relationship. Conditional analyses identified multiple independent secondary SNP associations ( P cond 0.05) around 28 BrCa and 22 PrCa CpGs. Cross-cancer analysis identified eight common CpGs, including a strong therapeutic target in SREBF1 (17p11.2)—a key player in lipid metabolism. These findings highlight the utility of integrative analysis of multi-omic cancer data to identify robust biomarkers and understand their regulatory effects on cancer risk.
Publisher: Springer Science and Business Media LLC
Date: 11-05-2022
DOI: 10.1038/S41467-022-30184-Z
Abstract: Migraine is a common complex disorder with a significant polygenic SNP heritability ( $${h}_{{SNP}}^{2}$$ h S N P 2 ). Here we utilise genome-wide association study (GWAS) summary statistics to study pleiotropy between blood proteins and migraine under the polygenic model. We estimate $${h}_{{SNP}}^{2}$$ h S N P 2 for 4625 blood protein GWASs and identify 325 unique proteins with a significant $${h}_{{SNP}}^{2}$$ h S N P 2 for use in subsequent genetic analyses. Pleiotropy analyses link 58 blood proteins to migraine risk at genome-wide, gene and/or single-nucleotide polymorphism levels—suggesting shared genetic influences or causal relationships. Notably, the identified proteins are largely distinct from migraine GWAS loci. We show that higher levels of DKK1 and PDGFB, and lower levels of FARS2, GSTA4 and CHIC2 proteins have a significant causal effect on migraine. The risk-increasing effect of DKK1 is particularly interesting—indicating a role for downregulation of β-catenin-dependent Wnt signalling in migraine risk, suggesting Wnt activators that restore Wnt/β-catenin signalling in brain could represent therapeutic tools against migraine.
Publisher: Elsevier BV
Date: 11-2021
Publisher: Elsevier BV
Date: 10-2021
Publisher: Springer Science and Business Media LLC
Date: 26-05-2017
DOI: 10.1007/S00280-017-3340-7
Abstract: ATP-binding cassette subfamily C member 4 (ABCC4) encoding MRP4 protein is involved in pediatric acute lymphoblastic leukemia (ALL) drug resistance. The nonsynonymous single nucleotide polymorphism (SNP) rs2274407 (G912T K304N) is located in the 3' splice acceptor site of exon 8 of ABCC4 pre-mRNA. The aim of this study was to investigate the prognostic value of rs2274407 in childhood ALL and its possible functional effect on MRP4. ABCC4 G912T SNP was genotyped in 145 Iranian Philadelphia-negative (Ph ABCC4 912T allele carriers (G/T and T/T genotypes) are associated with worse 3DFS in Pre-B cell ALL [P = 0.00019, OR (95% CI) = 13.17 (2.55-68.11)]. In addition, computational studies showed that K304N alteration has no impact on the MRP4 activity. However, it may disrupt the normal splicing process of ABCC4 pre-mRNA. To date, this is the first study that shows the potential functional impact of rs2274407 SNP on the aberrant splicing of ABCC4 mRNA. We also demonstrated a robust association between G912T and pediatric ALL negative outcome, which may be explained by the novel computational studies performed in this study.
Publisher: Elsevier BV
Date: 11-2016
Publisher: Elsevier BV
Date: 11-2021
Publisher: Spandidos Publications
Date: 31-03-2016
Abstract: ErbB4 can act as either a tumor-suppressor gene or an oncogene in breast cancer. Multiple genetic factors including single nucleotide polymorphisms (SNPs) affect gene expression patterns. Multiple 3'-untranslated region (3'-UTR) SNPs reside within the target binding site of microRNAs, which can strengthen or weaken binding to target genes. The present study aimed to predict potential 3'‑UTR variants of ErbB4 that alter the target binding site of microRNAs (miRNAs) and to clarify the association of the potential variant with the risk of developing breast cancer. In silico prediction was performed to identify potential functional SNPs within miRNA target binding sites in the 3'‑UTR of ErbB4. Thus, 146 patients and controls were genotyped using restriction fragment length polymorphism-polymerase chain reaction. In addition to the Cochran-Armitage test for trend, allele and genotype frequency differences were determined to investigate the association between rs1836724 and the susceptibility to breast cancer. Bioinformatics analysis identified rs1836724 to be a polymorphism in the seed region of four miRNA binding sites (hsa-miR335-5p, hsa-miR-28-5p, has‑miR‑708‑5p and has‑miR‑665), which may participate in the development of breast cancer. Logistic regression data indicated that the T allele of the polymorphism [OR (95% CI)=1.72 (1.056‑2.808), P=0.029] is associated with the risk of breast cancer. Using bioinformatics tools, a correlation was indicated between the presence of the T allele and a reduction in ErbB4 RNA silencing based on miRNA interaction. Furthermore, case subgroup data analysis revealed an association between the C/T genotype and an ER positive phenotype [OR (95% CI)=6.00 (1.082‑33.274), P=0.028] compared with the T/T genotype. ErbB4 and estrogen receptor 1 (ESR1) are regulated by identical miRNAs thus there may be a competition for binding sites. Due to this pattern, if the interaction between miRNAs with one gene is reduced, it may be consistent with the increase in interaction with another one. Therefore, more interaction with rs1836724 C variant within ErbB4 may be associated with higher expression of ESR1 (ER‑positive phenotype). miRNAs interact with ErbB4 mRNA more frequently when it carries C allele at the rs1836724 position compared with the T carriers. Therefore, the identical miRNA interacts with ESR1 less frequently when ErbB4 mRNA has a C allele. Therefore, ESR1 expression may be higher when ErbB4 mRNA has a C allele.
Publisher: Springer Science and Business Media LLC
Date: 17-11-2018
Publisher: Elsevier BV
Date: 11-2022
Publisher: Springer Science and Business Media LLC
Date: 28-09-2018
Publisher: Elsevier BV
Date: 08-2014
DOI: 10.1016/J.COMPBIOLCHEM.2014.05.002
Abstract: Aspirin (ASA) is a commonly used nonsteroidal anti-inflammatory drug (NSAID), which exerts its therapeutic effects through inhibition of cyclooxygenase (COX) isoform 2 (COX-2), while the inhibition of COX-1 by ASA leads to apparent side effects. In the present study, the relationship between COX-1 non-synonymous single nucleotide polymorphisms (nsSNPs) and aspirin related side effects was investigated. The functional impacts of 37 nsSNPs on aspirin inhibition potency of COX-1 with COX-1/aspirin molecular docking were computationally analyzed, and each SNP was scored based on DOCK Amber score. The data predicted that 22 nsSNPs could reduce COX-1 inhibition, while 15 nsSNPs showed increasing inhibition level in comparison to the regular COX-1 protein. In order to perform a comparing state, the Amber scores for two Arg119 mutants (R119A and R119Q) were also calculated. Moreover, among nsSNP variants, rs117122585 represented the closest Amber score to R119A mutant. A separate docking computation validated the score and represented a new binding position for ASA that acetyl group was located within the distance of 3.86Å from Ser529 OH group. This could predict an associated loss of activity of ASA through this nsSNP variant. Our data represent a computational sub-population pattern for aspirin COX-1 related side effects, and provide basis for further research on COX-1/ASA interaction.
Publisher: Elsevier BV
Date: 10-2016
DOI: 10.1016/J.MCP.2016.10.005
Abstract: MicroRNAs (miRNAs) are involved in the progression of breast cancer (BC). miR-9 has been reported to be correlated with either favorable or unfavorable events in BC. This study was aimed to evaluate the expression level of miR-9 in human breast tissues, including benign and malignant tumor s les and also healthy tissue. The expression level of miR-9 was analyzed in 10 normal breast tissues, 30 malignant, and 30 benign breast tumor tissue s les using RT-PCR and qPCR. In addition, bioinformatics assessment upon miR-9 functionality in BC cells was performed. The miR-9 expression level was downregulated in tumor tissues, including benign and malignant compared to the healthy tissue was observed (P value, < 0.0001 fold change, -1.37). In addition, miR-9 expression level was reduced in benign tumors compared with malignant tumors (P value, < 0.0001 fold change, -1.35). Moreover, according to the AUCs (area under curve) of receiver operating characteristic (ROC) curves, miR-9 showed significant capability for distinguishing benign from healthy, malignant from healthy, benign from malignant, and tumor from health tissues. Furthermore, pathways in cancer, p53 signaling pathway, and focal adhesion were manifested by computational analysis as miR-9 related signaling pathways which have logical association with experimental observations. In conclusion, downregulation of miR-9 in benign tumors vs healthy tissue and its overexpression in malignant tumors vs benign tumors suggest paradoxical functionality for this miRNA. Our results shed additional information on controversial expression pattern of miR-9 depending on different progression level of BC.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.CANCERGEN.2016.06.005
Abstract: Acute leukemia is the most common cancer in children and involves several factors that contribute to the development of multidrug resistance and treatment failure. According to our recent studies, the BAALC gene is identified to have high mRNA expression levels in childhood acute lymphoblastic leukemia (ALL) and those with multidrug resistance. Several polymorphisms are associated with the expression of this gene. To date, there has been no study on the rs62527607 [GT] single nucleotide polymorphism (SNP) of BAALC gene and its link with childhood acute lymphoblastic and myeloid leukemia (AML). The purpose of this study is to evaluate the prevalence of this polymorphism in pediatric acute leukemia, as well as its relationship with prognosis. DNA s les were extracted from bone marrow slides of 129 children with ALL and 16 children with AML. The rs62527607 [GT] SNP was evaluated using mismatch polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP)-based analysis. The association between the SNP alleles and patient disease-free survival was then assessed. The prevalence of the T-allele of rs62527607 [GT] SNP in childhood T-ALL and pre-B-ALL was 28.3% and 11.2%, respectively. In the pre-B-ALL patients, 3 year disease free survival was associated with the GG genotype. Results showed a robust association between the rs62527607 SNP and the risk of relapse in ALL, but not AML, patients. T-ALL patients with the GT genotype had an 8.75 fold higher risk of relapse. The current study demonstrates a significant association between the genotype GT and the polymorphic allele G424T, and introduces this SNP as a negative prognostic factor in children with ALL.
Publisher: Mary Ann Liebert Inc
Date: 12-2014
Publisher: Mary Ann Liebert Inc
Date: 03-2015
Abstract: Genotyping of single-nucleotide polymorphisms (SNPs) has been applied in various genetic contexts. Tetra-primer lification refractory mutation system (ARMS) polymerase chain reaction (PCR) is reported as a prominent assay for SNP genotyping. However, there were published data that may question the reliability of this method on some occasions, in addition to a laborious and time-consuming procedure of the optimization step. In the current study, a new SNP genotyping method named modified tetra-primer ARMS (MTPA) PCR was developed based on tetra-primer ARMS PCR. The modified method has two improvements in its instruction, including equalization of outer primer and inner primer strength by additional mismatch in outer primers, and consideration of equal annealing temperature of specific fragments more than melting temperature of primers. Advantageously, a new computer software was provided for designing primers based on novel concepts. The usual tetra-primer ARMS PCR has a laborious process for optimization. In nonoptimal PCR programs, identification of the accurate genotype was found to be very difficult. However, in MTPA PCR, equalization of the licons and primer strength leads to increasing specificity and convenience of genotyping, which was validated by sequencing. In the MTPA PCR technique, a new mismatch at -2 positions of outer primers and equal annealing temperature improve the genotyping procedure. Together, the introduced method could be suggested as a powerful tool for genotyping single-nucleotide mutations and polymorphisms.
Publisher: Wiley
Date: 10-2020
DOI: 10.1111/AGE.13003
No related grants have been discovered for Hamzeh TANHA.