ORCID Profile
0000-0001-7747-2530
Current Organisations
City, University of London
,
University of Technology Sydney
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Veterinary Sciences | Veterinary Parasitology
Expanding Knowledge in the Agricultural and Veterinary Sciences |
Publisher: Oxford University Press (OUP)
Date: 09-01-2008
DOI: 10.1093/HMG/DDN005
Abstract: Analysis of global microRNA (miRNA) expression in postmortem cortical grey matter from the superior temporal gyrus, revealed significant up-regulation of miR-181b expression in schizophrenia. This finding was supported by quantitative real-time RT-PCR analysis of miRNA expression in a cohort of 21 matched pairs of schizophrenia and non-psychiatric controls. The implications of this finding are substantial, as this miRNA is predicted to regulate many target genes with potential significance to the development of schizophrenia. They include the calcium sensor gene visinin-like 1 (VSNL1) and the ionotropic AMPA glutamate receptor subunit (GRIA2), which were found to be down-regulated in the same cortical tissue from the schizophrenia group. Both of these genes were also suppressed in miR-181b transfected cells and shown to contain functional miR-181b miRNA recognition elements by reporter gene assay. This study suggests altered miRNA levels could be a significant factor in the dysregulation of cortical gene expression in schizophrenia.
Publisher: Elsevier BV
Date: 09-2023
Publisher: Springer Science and Business Media LLC
Date: 24-03-2021
DOI: 10.1038/S41598-021-86125-1
Abstract: Fasciola hepatica , a global worm parasite of humans and their livestock, regulates host innate immune responses within hours of infection. Host macrophages, essential to the first-line defence mechanisms, are quickly restricted in their ability to initiate a classic protective pro-inflammatory immune response. We found that macrophages from infected animals are enriched with parasite-derived micro(mi)RNAs. The most abundant of these miRNAs, fhe-miR-125b , is released by the parasite via exosomes and is homologous to a mammalian miRNA, hsa-miR-125b , that is known to regulate the activation of pro-inflammatory M1 macrophages. We show that the parasite fhe-miR-125b loads onto the mammalian Argonaut protein (Ago-2) within macrophages during infection and, therefore, propose that it mimics host miR-125b to negatively regulate the production of inflammatory cytokines. The hijacking of the miRNA machinery controlling innate cell function could be a fundamental mechanism by which worm parasites disarm the early immune responses of their host to ensure successful infection.
Publisher: Springer Science and Business Media LLC
Date: 10-08-2020
DOI: 10.1186/S12936-020-03360-Z
Abstract: Extracellular vesicles (EVs) have been broadly studied in malaria for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microRNAs have numerous roles in host-parasite interactions and are considered promising biomarkers for disease severity. However, this field lacks clinical studies of malaria-infected s les. In this study, EV specific miRNAs were isolated from the plasma of patients from Thailand infected with Plasmodium vivax and Plasmodium falciparum . In addition, it is postulated that these miRNAs were differentially expressed in these groups of patients and had a role in disease onset through the regulation of specific target genes. EVs were purified from the plasma of Thai P. vivax -infected patients (n = 19), P. falciparum -infected patients (n = 18) and uninfected in iduals (n = 20). EV-derived miRNAs were then prepared and abundance of hsa-miR-15b-5p, hsa-miR-16-5p, hsa-let-7a-5p and hsa-miR-150-5p was assessed in these s les. Quantitative polymerase chain reaction was performed, and relative expression of each miRNA was calculated using hsa-miR-451a as endogenous control. Then, the targets of up-regulated miRNAs and relevant pathways were predicted by using bioinformatics. Receiver Operating Characteristic with Area under the Curve (AUC) was then calculated to assess their diagnostic potential. The relative expression of hsa-miR-150-5p and hsa-miR-15b-5p was higher in P. vivax -infected patients compared to uninfected in iduals, but hsa-let-7a-5p was up-regulated in both P. vivax -infected patients and P. falciparum -infected patients. Bioinformatic analysis revealed that these miRNAs might regulate genes involved in the malaria pathway including the adherens junction and the transforming growth factor-β pathways. All up-regulated miRNAs could potentially be used as disease biomarkers as determined by AUC however, the sensitivity and specificity require further investigation. An upregulation of hsa-miR-150-5p and hsa-miR-15b-5p was observed in P. vivax -infected patients while hsa-let-7a-5p was up-regulated in both P. vivax -infected and P. falciparum -infected patients. These findings will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EVs miRNAs to malaria detection and biology.
Publisher: Unpublished
Date: 2019
Publisher: IEEE
Date: 08-2014
Publisher: Springer Science and Business Media LLC
Date: 11-02-2016
Publisher: Wiley
Date: 2007
DOI: 10.1002/HED.20460
Abstract: Head and neck cancer is the world's sixth most common cancer, but despite advances in treatment, there has been no significant decline in the mortality rate. In recent years, there has been mounting epidemiologic and experimental evidence of a role for human papillomavirus (HPV) as the etiologic agent of a subset of head and neck cancers. The association is strongest for oropharyngeal cancers, especially those of the tonsil. HPV 16 is invariably the predominant type. HPV-positive cancers have been shown to be biologically distinct, clustering among nonsmokers and light drinkers, and have been associated with a favorable prognosis. This review examines the current findings of HPV in head and neck cancers and discusses implications for developing new treatments.
Publisher: American Society of Hematology
Date: 06-11-2014
Publisher: Wiley
Date: 08-03-2010
DOI: 10.1002/HED.21356
Abstract: A new class of regulatory molecules known as microRNAs (miRNAs) is redefining our understanding of the molecular pathways associated with tumorigenesis. These miRNAs are small noncoding RNA (ncRNA) sequences with potent regulatory potential. The aberrant expression of miRNAs has been associated with the development of various tumors. It has been suggested that miRNAs can both regulate and act as tumor-suppressor genes and oncogenes. Our understanding of the role of miRNAs in head and neck tumorigenesis is in its infancy. However, several recent studies have revealed extensive dysregulation of miRNA in head and neck tumors and have highlighted the potential of certain miRNAs to act as diagnostic and prognostic markers and targets for new therapeutic agents. The intent of this review is to discuss and summarize current findings that point to a significant role for miRNAs in head and neck tumorigenesis.
Publisher: Informa UK Limited
Date: 09-2019
DOI: 10.1128/MCB.00086-19
Publisher: Springer Science and Business Media LLC
Date: 04-06-2022
DOI: 10.1186/S12864-022-08644-Z
Abstract: MiRNAs are small non-coding RNAs that post-transcriptionally regulate gene expression in organisms ranging from viruses to mammals. There is great relevance in understanding how miRNAs regulate genes involved in the growth, development, and maturation of the many parasitic worms (helminths) that together afflict more than 2 billion people. Here, we describe the miRNAs expressed by each of the predominant intra-mammalian development stages of Fasciola hepatica , a foodborne flatworm that infects a wide range of mammals worldwide, most importantly humans and their livestock. A total of 124 miRNAs were profiled, 72 of which had been previously reported and three of which were conserved miRNA sequences described here for the first time. The remaining 49 miRNAs were novel sequences of which, 31 were conserved with F. gigantica and the remaining 18 were specific to F. hepatica. The newly excysted juveniles express 22 unique miRNAs while the immature liver and mature bile duct stages each express 16 unique miRNAs. We discovered several sequence variant miRNAs (IsomiRs) as well as miRNA clusters that exhibit strict temporal expression paralleling parasite development. Target analysis revealed the close association between miRNA expression and stage-specific changes in the transcriptome for ex le, we identified specific miRNAs that target parasite proteases known to be essential for intestinal wall penetration (cathepsin L3). Moreover, we demonstrate that miRNAs fine-tune the expression of genes involved in the metabolic pathways that allow the parasites to move from an aerobic external environment to the anerobic environment of the host. These results provide novel insight into the regulation of helminth parasite development and identifies new genes and miRNAs for therapeutic development to limit the virulence and pathogenesis caused by F. hepatica .
Publisher: Elsevier BV
Date: 12-2021
DOI: 10.1016/J.COVIRO.2021.09.013
Abstract: The Human Papillomavirus type 16 is a major etiologic factor for a subset of Head and Neck cancers. These cancers of the oropharyngeal region are growing, and it is expected to exceed cervical cancers in the near future. The major oncogenes E6 and E7 mediate many of the early transformation stages targeting p53 and other tumour suppressor genes. The majority of this regulation is centred on protein coding genes but more recently small non-coding RNAs, such as miRNAs are also regulated by HPV16. However, the system-wide impact of HPV16 on miRNAs is yet to be fully understood. To fully gauge the overall relationship between HPV16 and miRNAs, several studies have devised dynamic interactomes which encompass viral oncogenes, miRNAs and gene targets. These interactomes map potential pathways which permit the identification of possible mechanistic links. Our review will discuss the latest developments in using viral interactomes to understand viral mechanisms and how these approaches may aid in the elucidation of potential druggable pathways.
Publisher: Springer Science and Business Media LLC
Date: 22-04-2016
DOI: 10.1038/SREP24922
Abstract: Long non-coding RNAs (lncRNAs) form the largest transcript class in the human transcriptome. These lncRNA are expressed not only in the cells, but they are also present in the cell-derived extracellular vesicles such as exosomes. The function of these lncRNAs in cancer biology is not entirely clear, but they appear to be modulators of gene expression. In this study, we characterize the expression of lncRNAs in several prostate cancer exosomes and their parental cell lines. We show that certain lncRNAs are enriched in cancer exosomes with the overall expression signatures varying across cell lines. These exosomal lncRNAs are themselves enriched for miRNA seeds with a preference for let-7 family members as well as miR-17, miR-18a, miR-20a, miR-93 and miR-106b. The enrichment of miRNA seed regions in exosomal lncRNAs is matched with a concomitant high expression of the same miRNA. In addition, the exosomal lncRNAs also showed an over representation of RNA binding protein binding motifs. The two most common motifs belonged to ELAVL1 and RBMX. Given the enrichment of miRNA and RBP sites on exosomal lncRNAs, their interplay may suggest a possible function in prostate cancer carcinogenesis.
Publisher: The Company of Biologists
Date: 04-2021
DOI: 10.1242/DMM.047662
Abstract: Canonically, microRNAs (miRNAs) control mRNA expression. However, studies have shown that miRNAs are also capable of targeting non-coding RNAs, including long non-coding RNAs and miRNAs. The latter, termed a miRNA:miRNA interaction, is a form of self-regulation. In this Review, we discuss the three main modes of miRNA:miRNA regulation: direct, indirect and global interactions, and their implications in cancer biology. We also discuss the cell-type-specific nature of miRNA:miRNA interactions, current experimental approaches and bioinformatic techniques, and how these strategies are not sufficient for the identification of novel miRNA:miRNA interactions. The self-regulation of miRNAs and their impact on gene regulation has yet to be fully understood. Investigating this hidden world of miRNA self-regulation will assist in discovering novel regulatory mechanisms associated with disease pathways.
Publisher: Elsevier BV
Date: 07-2016
DOI: 10.1016/J.TRECAN.2016.05.008
Abstract: miRNAs modulate gene expression while exosomes are extracellular cargo vessels that transport miRNAs and other materials to surrounding cells. When exosomes are taken up by recipient cells, the released miRNAs can modulate immune responses, inhibit apoptosis, and promote angiogenesis to maintain tumor growth. Central to this regulation is the processing of the primary transcripts into active miRNAs, which occurs exclusively within mammalian cells. Challenging this dogma is the discovery that Dicer and Ago2, key components of miRNA processing, are also present inside exosomes. While the exact nature of this processing requires extensive proof, it is an exciting notion that exogenous miRNA factories could exist outside the canonical boundaries of mammalian cells.
Publisher: Elsevier BV
Date: 06-2016
Publisher: Elsevier BV
Date: 04-2007
DOI: 10.1080/00313020701230823
Abstract: Our previous studies of tonsillar cancers from New South Wales, Australia, and Jilin Province in the north-east of China, provided evidence that the proportion of these cancers attributable to human papillomavirus (HPV) varies geographically. This study provides the first data on HPV in tonsillar cancers from Hong Kong. A total of 49 Hong Kong tonsillar cancers were analysed for HPV DNA by PCR/sequencing and for p16(INK4A), retinoblastoma (pRb) protein, cyclin D1 and p53 expression by semiquantitative immunohistochemistry as evidence of virus causality. Results were compared with those from New South Wales and Jilin Province. Of the 31 Hong Kong cancers with lifiable DNA, nine (29%) were HPV positive by PCR compared with 46% from New South Wales and 0% from Jilin Province. HPV positivity correlated with female gender, young age, over-expression of p16(INK4A) and loss of pRb and cyclin D1. Five-year disease-specific survival for patients with HPV positive and HPV negative cancers was 82 and 42%, respectively. Relationships between HPV status and cell protein expression in Hong Kong cancers were consistent with those from New South Wales and Jilin Province. The proportion of HPV-associated cancers reflected the relative incidence of oropharyngeal cancer in these regions. HPV is responsible for a small proportion of tonsillar cancers in Hong Kong patients. Differences in the proportions of tumours attributable to HPV in Hong Kong, New South Wales and Jilin Province may be due to environmental, cultural or genetic factors in the different populations.
Publisher: Frontiers Media SA
Date: 29-01-2021
DOI: 10.3389/FIMMU.2020.608686
Abstract: Understanding mechanisms by which parasitic worms (helminths) control their hosts’ immune responses is critical to the development of effective new disease interventions. Fasciola hepatica , a global scourge of humans and their livestock, suppresses host innate immune responses within hours of infection, ensuring that host protective responses are quickly incapacitated. This allows the parasite to freely migrate from the intestine, through the liver to ultimately reside in the bile duct, where the parasite establishes a chronic infection that is largely tolerated by the host. The recent identification of micro(mi)RNA, small RNAs that regulate gene expression, within the extracellular vesicles secreted by helminths suggest that these non-coding RNAs may have a role in the parasite-host interplay. To date, 77 miRNAs have been identified in F. hepatica comprising primarily of ancient conserved species of miRNAs. We hypothesized that many of these miRNAs are utilized by the parasite to regulate host immune signaling pathways. To test this theory, we first compiled all of the known published F. hepatica miRNAs and critically curated their sequences and annotations. Then with a focus on the miRNAs expressed by the juvenile worms, we predicted gene targets within human innate immune cells. This approach revealed the existence of targets within every immune cell, providing evidence for the universal management of host immunology by this parasite. Notably, there was a high degree of redundancy in the potential for the parasite to regulate the activation of dendritic cells, eosinophils and neutrophils, with multiple miRNAs predicted to act on singular gene targets within these cells. This original exploration of the Fasciola miRnome offers the first molecular insight into mechanisms by which F. hepatica can regulate the host protective immune response.
Publisher: Springer International Publishing
Date: 2022
DOI: 10.1007/978-3-031-08356-3_9
Abstract: MicroRNAs (miRNAs) are known for their role in the post-transcriptional regulation of messenger RNA (mRNA). However, recent evidence has shown that miRNAs are capable of regulating non-coding RNAs, including miRNAs, in what is known as miRNA:miRNA interactions. There are three main models for the interplay between miRNAs. These involve direct interaction between two miRNAs, either in their mature or primary form, the subsequent changes in miRNA expression due to miRNA-directed transcriptional changes, and the cell-wide impact on miRNA and mRNA levels as a result of miRNA manipulation. Networks of mRNA and miRNA regulatory connections are invaluable to the discovery of miRNA:miRNA pathways, but this cannot be applied without consideration of the specific cell type or condition.In this chapter, we discuss what is understood about miRNA:miRNA interactions, their mechanisms and consequences in disease biology, and suggest further avenues of investigation based on current gaps in the literature and in our understanding of miRNA biology. We also address the pitfalls in contemporary methods relating to the identification of miRNA:miRNA interactions. Future work in this area may ultimately change the definitional role of miRNAs, and have far-reaching impacts on therapeutic and diagnostic developments.
Publisher: Springer Science and Business Media LLC
Date: 19-10-2012
Abstract: MicroRNA (miRNA) are small non-coding RNA molecules which function as nucleic acid-based specificity factors in the universal RNA binding complex known as the RNA induced silencing complex (RISC). In the canonical gene-silencing pathway, these activated RISC particles are associated with RNA decay and gene suppression, however, there is evidence to suggest that in some circumstances they may also stabilise their target RNA and even enhance translation. To further explore the role of miRNA in this context, we performed a genome-wide expression analysis to investigate the molecular consequences of bidirectional modulation of the disease-associated miRNAs miR-181b and miR-107 in multiple human cell lines. This data was subjected to pathways analysis and correlated against miRNA targets predicted through seed region homology. This revealed a large number of both conserved and non-conserved miRNA target genes, a selection of which were functionally validated through reporter gene assays. Contrary to expectation we also identified a significant proportion of predicted target genes with both conserved and non-conserved recognition elements that were positively correlated with the modulated miRNA. Finally, a large proportion of miR-181b associated genes devoid of the corresponding miRNA recognition element, were enriched with binding motifs for the E2F1 transcription factor, which is encoded by a miR-181b target gene. These findings suggest that miRNA regulate target genes directly through interactions with both conserved and non-conserved target recognition elements, and can lead to both a decrease and increase in transcript abundance. They also multiply their influence through interaction with transcription factor genes exemplified by the observed miR-181b/E2F1 relationship.
Publisher: Elsevier BV
Date: 2021
Publisher: Public Library of Science (PLoS)
Date: 09-03-2009
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.RADI.2022.07.002
Abstract: The Radiography Research Ethics Standards for Europe (RRESFE) project aims to provide a cross-sectional snapshot of current research ethics systems, processes, and awareness of such, across Europe together with identifying the associated challenges, education, and training needs. A cross-sectional online survey targeting radiography researchers in Europe was conducted. Data collection took place between April 26 and July 12, 2021, using a snowball s ling approach. Descriptive and analytical statistics were used to identify trends in research ethics frameworks across Europe. 285 responses were received across 33 European and 23 non-European countries. Most (n = 221 95%) European respondents stated ethics approval is required before commencing research in their country. Requirements around research ethics approval and awareness of such requirements varied by European region (X Respondents from countries with longer programme durations/availability of multiple programme lengths, availability of postgraduate training, and establishment of European Qualifications Framework Level 6 were generally associated with less uncertainty and more comprehensive research ethics requirements. Results are informative of the current status of research ethics within evidence-based radiography.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.RADI.2022.07.004
Abstract: The Radiography Research Ethics Standards for Europe (RRESFE) project aimed to provide a cross-sectional view of the current state of radiography research ethics across Europe. This included investigating education and training in research ethics, and identifying the key challenges and potential improvements associated with using existing research ethics frameworks. This cross-sectional online survey targeting radiography researchers in Europe was conducted between April 26 and July 12, 2021. Descriptive and analytical statistics were used to identify research ethics education and training trends. Content analysis of qualitative responses was employed to identify significant challenges and proposed improvements in research ethics frameworks of practice. There were 232 responses received across 33 European countries. Most (n = 132 57%) respondents had received some research ethics training however, fewer participants had received training on safeguarding vulnerable patients (n = 72 38%), ersity and inclusivity (n = 62 33%), or research with healthy volunteers (n = 60 32%). Training was associated with a greater perceived importance of the need for research ethics review (p = 0.031) and with the establishment of EQF Level 6 training (p = 0.038). The proportion of formally trained researchers also varied by region (p = <0.001). Time-to-ethics-approval was noted as the biggest challenge for professionals making research ethics applications. Early and universal integration of research-oriented teaching within the radiography education framework which emphasises research ethics is recommended. Additionally, study findings suggest research ethics committee application and approval processes could be further simplified and streamlined. The survey contributes to a growing body of knowledge surrounding the importance of education and training in research ethics for assuring a high standard of research outputs in Radiography and has identified hurdles to obtaining research ethics approval for further investigation and address.
Publisher: SAGE Publications
Date: 28-12-2021
DOI: 10.1177/13623613211065542
Abstract: Magnetic resonance imaging is widely used for different diagnostic examinations involving autistic patients. The noisy, narrow, isolating magnetic resonance imaging environment and long scan times may not be suitable for autistic in iduals, given their communication challenges, sensory sensitivities and often heightened anxiety. This systematic review aims to reveal any reasonable and feasible radiography-based adjustments to facilitate magnetic resonance imaging scanning without the use of sedation or general anaesthesia. Nine electronic databases were systematically searched. Out of 4442 articles screened, 53 were deemed directly relevant when assessed against eligibility criteria, only 21 were finally included in this systematic review. Customising communication was found to be a key adjustment, as well as scan-based optimisation and environmental adaptations. The importance of distraction techniques and use of technology for familiarisation with the processes was also highlighted. The results of this study can inform recommendations to improve magnetic resonance imaging practice and patient experience, without the use of sedation or anaesthesia, where feasible. They can also inform the basis of dedicated training for magnetic resonance imaging radiographers. Autistic patients often undergo magnetic resonance imaging examinations. Within this environment, it is usual to feel anxious and overwhelmed by noises, lights or other people. The narrow scanners, the loud noises and the long examination time can easily cause panic attacks. This review aims to identify any adaptations for autistic in iduals to have a magnetic resonance imaging scan without sedation or anaesthesia. Out of 4442 articles screened, 53 more relevant were evaluated and 21 were finally included in this study. Customising communication, different techniques to improve the environment, using technology for familiarisation and distraction have been used in previous studies. The results of this study can be used to make suggestions on how to improve magnetic resonance imaging practice and the autistic patient experience. They can also be used to create training for the healthcare professionals using the magnetic resonance imaging scanners.
Publisher: Public Library of Science (PLoS)
Date: 25-04-2013
Publisher: Elsevier BV
Date: 07-2018
DOI: 10.1016/J.TRECAN.2018.05.002
Abstract: MicroRNAs (miRNA) are capable of self-regulation, termed miRNA to miRNA interaction. Very little is known about these interactions and their impact on the cellular milieu. We discuss known miRNA to miRNA interactions, potential mechanisms, and their role in cancer.
Publisher: Portland Press Ltd.
Date: 30-04-2013
DOI: 10.1042/BSE0540017
Abstract: Regulation of gene expression is a fundamental process in both prokaryotic and eukaryotic organisms. Multiple regulatory mechanisms are in place to control gene expression at the level of transcription, post-transcription and post-translation to maintain optimal RNA and protein expressions in cells. miRNAs (microRNAs) are abundant short 21–23 nt non-coding RNAs that are key regulators of virtually all eukaryotic biological processes. The levels of miRNAs in an organism are crucial for proper development and sustaining optimal cell functions. Therefore the processing and regulation of the processing of these miRNAs are critical. In the present chapter we highlight the most important steps of miRNA processing, describe the functions of key proteins involved in the maturation of miRNAs, and discuss how the generation and the stability of miRNAs are regulated.
Publisher: Elsevier BV
Date: 12-2021
Abstract: MicroRNAs (miRNAs) are a class of noncoding RNAs that contribute to a broad range of biological processes through post-transcriptional regulation of gene expression. Helminths exploit this system to target mammalian gene expression, to modulate the host immune response. Recent discoveries have shed new light on the mechanisms involved.
Publisher: Elsevier BV
Date: 12-2009
DOI: 10.1016/J.CELLSIG.2009.07.019
Abstract: Whole-genome microRNA and gene expression analyses were used to monitor changes during retinoic acid induced differentiation of neuroblasts in vitro. Interestingly, the entire miR-17 family was over-represented among the down-regulated miRNA. The implications of these changes are considerable, as target gene prediction suggests that the miR-17 family is involved in the regulation of the mitogen-activated protein kinase (MAPK) signaling pathway, synaptic plasticity and other markers of neuronal differentiation. Significantly, many of the target responses predicted by changes in miRNA expression were supported by the observed changes in gene expression. As expected, markers of neuronal differentiation such as anti-apoptotic protein B-cell lymphoma 2 (BCL2), myocyte enhancer factor-2D (MEF2D) and zipper protein kinase (MAP3K12 aka ZPK/MUK/DLK) were each up-regulated in response to differentiation. The expression of these genes was also reduced in response to miR-17 and miR-20a transfection, and more specifically they were also shown to contain functional miRNA recognition elements for members of the miR-17 family by reporter gene assay. This suggests that the miR-17 family have an integral role in fine-tuning the pathways involved in the regulation of neuronal differentiation.
Publisher: BMJ
Date: 09-2009
Abstract: Pleomorphic adenomas of the salivary gland have gender and age distributions suggesting that oestrogen has a causal role. However, oestrogen receptor (ER)alpha is expressed at low levels in normal salivary gland tissues and data from salivary gland tumours are conflicting. There is preliminary evidence that the recently described ERbeta may be the major ER in salivary gland tissue. The aim of this study was to determine the nature and extent of ERbeta expression in pleomorphic adenomas of the salivary gland. Pleomorphic adenomas and normal tissues of the parotid gland from 49 patients were tested for ERalpha and ERbeta expression by semiquantitative immunohistochemistry. Associations were sought with patient age and gender. ERalpha and ERbeta expression was localised mainly to the nuclei of ductal cells in normal tissues and the epithelial components in pleomorphic adenomas. Within each tissue and receptor type there were no associations between ER positivity and patient age or gender. ERbeta was expressed in almost twice as many normal tissues and pleomorphic adenomas as ERalpha. Expression of ERbeta was also significantly higher in tumour compared with normal tissues. This is thought to be the first study of ERbeta in pleomorphic adenomas of the salivary gland. Findings support ERbeta as the major ER in salivary glands, and provide evidence that ERbeta may have a role in the development of pleomorphic adenomas of the salivary gland.
Publisher: Future Medicine Ltd
Date: 02-2015
DOI: 10.2217/BMM.14.102
Abstract: MicroRNAs (miRNAs) belong to a class of small noncoding RNAs (ncRNAs), which regulate gene expression at the post-transcriptional level. They are approximately 22 nucleotide sequences in length and have been predicted to control expression of up to 30–60% of all protein-coding genes in mammals. Considering this wide involvement in gene control, aberrant miRNA expression has a strong association with the presence and progression of a disease, hence generating much anticipation in using miRNAs as biomarkers for the diagnosis and prognosis of human cancers. The majority of these miRNAs are intracellular, but recently they have been discovered in bodily fluids. This review will provide an insight into these circulatory miRNA molecules and discuss their potential as cancer biomarkers.
Publisher: IEEE
Date: 08-2016
Publisher: Elsevier BV
Date: 2020
Publisher: Springer Science and Business Media LLC
Date: 2003
Publisher: Elsevier BV
Date: 08-2018
DOI: 10.1016/J.VIROL.2018.05.022
Abstract: Human papillomavirus (HPV), notably type 16, is a risk factor for up to 75% of oropharyngeal squamous cell carcinomas (SCC). It has been demonstrated that small non-coding RNAs known as microRNAs play a vital role in the cellular transformation process. In this study, we used an LNA array to further investigate the impact of HPV16 on the expression of microRNAs in oropharyngeal (tonsillar) cancer. A number of miRNAs were found to be deregulated, with miR-496 showing a four-fold decrease. Over-expression of the high risk E6 oncoprotein down-regulated miR-496, impacting upon the post-transcriptional control of the transcription factor E2F2. These HPV specific miRNAs were integrated with the HPV16 interactome to identify possible mechanistic pathways. These analyses provide insights into novel molecular interactions between HPV16 and miRNAs in oropharyngeal cancers.
Publisher: Springer Science and Business Media LLC
Date: 20-10-2009
Abstract: MicroRNAs (MiRNAs) are short non-coding RNAs that control protein expression through various mechanisms. Their altered expression has been shown to be associated with various cancers. The aim of this study was to profile miRNA expression in colorectal cancer (CRC) and to analyze the function of specific miRNAs in CRC cells. MirVana miRNA Bioarrays were used to determine the miRNA expression profile in eight CRC cell line models, 45 human CRC s les of different stages, and four matched normal colon tissue s les. SW620 CRC cells were stably transduced with miR-143 or miR-145 expression vectors and analyzed in vitro for cell proliferation, cell differentiation and anchorage-independent growth. Signalling pathways associated with differentially expressed miRNAs were identified using a gene set enrichment analysis. The expression analysis of clinical CRC s les identified 37 miRNAs that were differentially expressed between CRC and normal tissue. Furthermore, several of these miRNAs were associated with CRC tumor progression including loss of miR-133a and gain of miR-224. We identified 11 common miRNAs that were differentially expressed between normal colon and CRC in both the cell line models and clinical s les. In vitro functional studies indicated that miR-143 and miR-145 appear to function in opposing manners to either inhibit or augment cell proliferation in a metastatic CRC model. The pathways targeted by miR-143 and miR-145 showed no significant overlap. Furthermore, gene expression analysis of metastatic versus non-metastatic isogenic cell lines indicated that miR-145 targets involved in cell cycle and neuregulin pathways were significantly down-regulated in the metastatic context. MiRNAs showing altered expression at different stages of CRC could be targets for CRC therapies and be further developed as potential diagnostic and prognostic analytes. The identified biological processes and signalling pathways collectively targeted by co-expressed miRNAs in CRC provide a basis for understanding the functional role of miRNAs in cancer.
Publisher: IEEE
Date: 08-2006
Publisher: Elsevier BV
Date: 02-2022
DOI: 10.1016/J.RADI.2021.09.003
Abstract: Autistic in iduals undergoing magnetic resonance imaging (MRI) examinations may face significant challenges, mainly due to sensory overload and MRI environment-related limitations. This study aimed to explore radiographers' perspectives and experiences regarding MRI scanning of autistic in iduals. Data collection was achieved using a specifically designed mixed methods questionnaire on Qualtrics. The snowball technique was used. This UK-wide survey was electronically distributed by three main recruitment agencies between December 2020 and February 2021. 130 valid responses were received. A lack of relevant training and knowledge related to autism was noted. Effective communication, optimisation and customisation of the MRI examination, and MRI environment adjustments facilitated the completion of a safe and effective MRI examination. Poor patient-radiographer communication, unavailability of Special Educational Needs (SEN) experts, lack of specialised radiographer training and lack of specific guidelines were identified as the main barriers to successful MRI examinations. Although routine MRI safety and patient care rules will apply, MRI scanning of autistic in iduals requires customisation and reasonable adjustments in communication, environment, and training of clinical teams. In addition, guidelines should be established to be used as a reference point to improve clinical practice. The adjustments proposed by radiographers were all consistent with the interventions in the wider literature. MRI practice for personalised care of autistic in iduals should be aligned with current evidence, to customise communication and offer workflow and environmental adjustments. Formal training related to autism, integrated within radiography academic curricula and better co-ordination and communication of interdisciplinary teams would provide the necessary skill mix to deliver safe, high quality MRI scans with optimal experience for autistic service users and their carer(s).
Publisher: MyJove Corporation
Date: 19-06-2014
DOI: 10.3791/51443
Publisher: Ovid Technologies (Wolters Kluwer Health)
Date: 27-08-2006
Publisher: American Society of Hematology
Date: 17-10-2013
DOI: 10.1182/BLOOD-2012-12-473017
Abstract: Blockmirs are designed against the miR-27 binding site in VE-cadherin and display restricted specificity. Blockmirs regulate VE-cadherin and endothelial cell junctions, inhibit edema, and promote angiogenesis associated with ischemia.
Publisher: Wiley
Date: 20-07-2020
DOI: 10.1002/HED.26348
Publisher: Wiley
Date: 09-08-2004
Publisher: Wiley
Date: 03-04-2009
DOI: 10.1002/IJC.24298
Abstract: Genome-wide microRNA (miRNA) expression profiling of salivary gland pleomorphic adenomas revealed a distinct expression signature consisting largely of upregulated miRNAs compared with matched normal tissue. Microarray data were confirmed by quantitative real time RT-PCR (q-RTPCR). Five miRNA genes upregulated in the tumours were found in close proximity to fragile sites and/or cancer associated genomic regions. Interestingly, q-RTPCR revealed an increase in the expression of components of the miRNA processing machinery (Dicer, Drosha, DGCR8 and p68) in tumours suggesting that the deregulation of miRNA expression may result from increased miRNA biogenesis. Target gene prediction analysis of the altered miRNAs indicated that genes in a number of signalling pathways important in tumourigenesis including WNT, MAPK and JAK-STAT were overrepresented. Significantly, the oncogene PLAG1 was overexpressed in our cohort and may be potentially regulated by these miRNAs. This is the first study to examine changes in the miRNA milieu in pleomorphic adenoma, the most common salivary gland tumour. This study has demonstrated an upregulation of both miRNAs genes and an upregulation of the miRNA processing machinery. These changes may be potential underlying mechanisms for the development of these benign tumours.
Publisher: Bioscientifica
Date: 06-1999
Abstract: The mammalian testis-determining gene Sry and the related Sox genes define a family of transcriptional regulators widely expressed during embryogenesis. Tightly controlled temporal profiles of expression are a feature of the Sox gene family and may be required for initiation of a cascade of gene expression, yet the molecular mechanisms that control Sox gene expression are unknown. We now show that human SOX4 is expressed in the normal breast and in breast cancer cells. In these cells SOX4 is a progesterone-regulated gene, the expression of which is increased by progestins, leading to a marked increase in SOX-mediated transcriptional activity. Treatment of T-47D breast cancer cells with the synthetic progestin ORG 2058 directly increased SOX4 transcription, resulting in a 4-fold increase in SOX4 mRNA levels within 4 h of treatment. No effect of ORG 2058 was noted on other SOX genes measured, nor were other hormone-regulated HMG box proteins detected in this system, suggesting that the observed ability of progestin to increase SOX mRNA expression was confined to SOX4. The increase in SOX4 transcription was reflected in increased SOX4 protein expression, as progestin treatment of T-47D cells transfected with a SOX-responsive reporter resulted in a marked increase in reporter gene expression. Progesterone is essential for normal development and differentiation of the female reproductive system, plays an essential role in regulating growth and differentiation of the mammary gland and is required for opposing the proliferative effects of estrogen in specific cell types. The detection of SOX4 expression in the normal and malignant breast and the demonstration that SOX4 expression is under progesterone control suggests that changes in SOX4 gene expression may play a role in commitment to the differentiated phenotype in the normal and malignant mammary gland.
Publisher: MDPI AG
Date: 20-08-2023
Abstract: Locally advanced rectal cancer (LARC) has traditionally been treated with trimodality therapy consisting of neoadjuvant radiation +/− chemotherapy, surgery, and adjuvant chemotherapy. There is currently a clinical need for biomarkers to predict treatment response and outcomes, especially during neoadjuvant therapy. Liquid biopsies in the form of circulating tumour cells (CTCs) and circulating nucleic acids in particular microRNAs (miRNA) are novel, the latter also being highly stable and clinically relevant regulators of disease. We studied a prospective cohort of 52 patients with LARC, and obtained s les at baseline, during treatment, and post-treatment. We enumerated CTCs during chemoradiation at these three time-points, using the IsofluxTM (Fluxion Biosciences Inc., Alameda, CA, USA) CTC Isolation and detection platform. We then subjected the isolated CTCs to miRNA expression analyses, using a panel of 106 miRNA candidates. We identified CTCs in 73% of patients at baseline numbers fell and miRNA expression profiles also changed during treatment. Between baseline and during treatment (week 3) time-points, three microRNAs (hsa-miR-95, hsa-miR-10a, and hsa-miR-16-1*) were highly differentially expressed. Importantly, hsa-miR-19b-3p and hsa-miR-483-5p were found to correlate with good response to treatment. The latter (hsa-miR-483-5p) was also found to be differentially expressed between good responders and poor responders. These miRNAs represent potential predictive biomarkers, and thus a potential miRNA-based treatment strategy. In this study, we demonstrate that CTCs are present and can be isolated in the non-metastatic early-stage cancer setting, and their associated miRNA profiles can potentially be utilized to predict treatment response.
Publisher: Elsevier BV
Date: 12-2022
Publisher: Springer Science and Business Media LLC
Date: 03-2002
Abstract: Progesterone receptor (PR) mediates the effects of progesterone in mammary tissues and plays a crucial role in normal breast development and in breast cancer. PR proteins are expressed as two isoforms, PRA and PRB, that have different capacities to activate target genes, yet it is unknown whether progesterone action in normal and malignant breast is mediated by PRA and/or PRB. This study determines the relative expression of PRA and PRB in normal breast and in benign, premalignant and malignant archival breast lesions by dual immunofluorescent histochemistry. In normal breast and in proliferative disease without atypia (PDWA) PRA and PRB were co-expressed within the same cells in comparable amounts, implicating both isoforms in progesterone action. In atypical lesions, however, there was a significant increase in predominant expression of PRA or PRB, with lesion progression from the normal state to malignancy. PR isoform predominance, especially PRA predominance, was evident in a high proportion of ductal carcinomas in situ (DCIS) and invasive breast lesions. In the normal breast and in PDWA, the relative expression of PRA and PRB in adjacent cells was homogenous. There was a significant increase in cell-to-cell heterogeneity of PR isoform expression in ADH and DCIS lesions and in the majority of breast cancers. Heterogeneous cell-to-cell expression of PR isoforms occurred prior to overall predominant expression of one isoform in premalignant breast lesions, demonstrating that loss of control of relative PRA:PRB expression is an early event in the development of breast cancer. PRA:PRB ratios within a breast lesion are likely to be important as both markers and effectors of tumor growth and development, and progressively aberrant PR isoform expression may play a role in the etiology of breast cancer.
Publisher: Research Square Platform LLC
Date: 24-03-2020
DOI: 10.21203/RS.3.RS-18294/V1
Abstract: Background Extracellular vesicles (EVs) have been broadly studied in malaria for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microRNAs have numerous roles in host-parasite interactions and are considered as promising biomarkers for disease severity. However, this field lacks clinical studies of malaria-infected s les. In our study, we investigated EV specific miRNAs isolated from the plasma of patients from Thailand infected with Plasmodium falciparum and Plasmodium vivax . We postulated that these miRNAs were differentially expressed in these groups of patients and had a role in disease onset through the regulation of specific target genes. Methods EVs were purified from the plasma of Thai P.vivax -infected patients (PV, n=19), P.falciparum -infected patients (PF, n=18) and uninfected in iduals (n=20). EV-derived miRNAs were then prepared and abundance of miR-15b-5p, hsa-miR-16-5p, hsa-let-7a-5p and hsa-miR-150-5p was assessed in these s les. Quantitative Polymerase Chain Reaction was performed, and relative expression of each miRNA was calculated using hsa-miR-451a as endogenous control. We then predicted the targets of up-regulated miRNAs and relevant pathways by bioinformatics. Receiver Operating Characteristic with Area Under the Curve (AUC) was then calculated to assess their diagnostic potential. Results The relative expression of hsa-miR-150-5p and hsa-miR-15b-5p was higher in PV patients compared to uninfected in iduals, but hsa-let-7a-5p was up-regulated in both PV and PF. Bioinformatic analysis revealed that these miRNAs might regulate genes involved in the malaria pathway including the Adherens junction and the transforming growth factor-β pathways. All up-regulated miRNAs could potentially be used as disease biomarker as determined by AUC however, the sensitivity and specificity require further investigation. Conclusion The up-regulated hsa-miR-150-5p and hsa-miR-15b-5p in PV, hsa-let-7a-5p in both PV and PF may play a role in host-parasite interactions. The findings in this study will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EV miRNAs to malaria detection and biology.
Publisher: Research Square Platform LLC
Date: 10-08-2020
DOI: 10.21203/RS.3.RS-18294/V2
Abstract: Background Extracellular vesicles (EVs) have been broadly studied in malaria for nearly a decade. These vesicles carry various functional biomolecules including RNA families such as microRNAs (miRNA). These EVs-derived microRNAs have numerous roles in host-parasite interactions and are considered promising biomarkers for disease severity. However, this field lacks clinical studies of malaria-infected s les. In this study, EV specific miRNAs were isolated from the plasma of patients from Thailand infected with Plasmodium vivax and Plasmodium falciparum . In addition, it is postulated that these miRNAs were differentially expressed in these groups of patients and had a role in disease onset through the regulation of specific target genes. Methods EVs were purified from the plasma of Thai P. vivax -infected patients (n=19), P. falciparum -infected patients (n=18) and uninfected in iduals (n=20). EV-derived miRNAs were then prepared and abundance of hsa-miR-15b-5p, hsa-miR-16-5p, hsa-let-7a-5p and hsa-miR-150-5p was assessed in these s les. Quantitative polymerase chain reaction was performed, and relative expression of each miRNA was calculated using hsa-miR-451a as endogenous control. Then, the targets of up-regulated miRNAs and relevant pathways were predicted by using bioinformatics. Receiver Operating Characteristic with Area Under the Curve (AUC) was then calculated to assess their diagnostic potential. Results The relative expression of hsa-miR-150-5p and hsa-miR-15b-5p was higher in P. vivax -infected patients compared to uninfected in iduals, but hsa-let-7a-5p was up-regulated in both P. vivax -infected patients and P. falciparum -infected patients. Bioinformatic analysis revealed that these miRNAs might regulate genes involved in the malaria pathway including the adherens junction and the transforming growth factor-β pathways. All up-regulated miRNAs could potentially be used as disease biomarkers as determined by AUC however, the sensitivity and specificity require further investigation. Conclusion An upregulation of hsa-miR-150-5p and hsa-miR-15b-5p was observed in P. vivax -infected patients while hsa-let-7a-5p was up-regulated in both P. vivax -infected and P. falciparum -infected patients. These findings will require further validation in larger cohort groups of malaria patients to fully understand the contribution of these EVs miRNAs to malaria detection and biology.
Publisher: Elsevier BV
Date: 11-2022
DOI: 10.1016/J.CTRV.2022.102439
Abstract: Clinically, HPV-positive oropharyngeal cancers (OPCs) have been shown to have a distinct prognosis, compared to HPV-negative tumours, particularly in survival rates and responses to treatment. These patients have better survival chances and improved prognosis, indicating that a more exhaustive knowledge of these distinctions would aid in the discovery of clinical approaches for both HPV-positive and negative tumours. Furthermore, there is increasing evidence that HPV-related oropharyngeal cancers constitute an epidemiological, molecular, and clinical distinct form as compared to non-HPV related ones therefore, the treatment of these specific subtype of oropharyngeal cancers should adopt a distinct clinical treatment pipeline. Our review will examine the current approaches for the diagnosis and treatment of OPC and discuss the relevance of de-escalation clinical trials in progress.
Publisher: Elsevier BV
Date: 06-2007
DOI: 10.1016/J.BBRC.2007.03.201
Abstract: Non-coding RNA molecules such as microRNAs (miRNAs) may play an important role in human carcinogenesis. Their expression has been profiled in many human cancers but there are few published studies in head and neck cancer. In this study, the relative expression of 261 mature miRNA genes was determined in nine head and neck cancer cell lines using an oligonucleotide array platform. Thirty-three miRNAs in the array were found to be highly expressed and 22 showed low levels of expression in all cell lines. Notable was the high expression of miR-21 and miR-205. Expression of several miRNAs was validated using Northern blot analysis. Potential targets of validated miRNAs included tumor suppressor genes, kinesin family member 1B isoform alpha (KIF1B), and hypermethylated in cancer 2 (HIC2), and pleomorphic adenoma gene 1 (PLAG1). This study provides the largest genomewide survey of mature miRNA transcripts in head and neck cancer cell lines.
Publisher: Elsevier BV
Date: 09-2016
Publisher: PeerJ
Date: 25-06-2020
DOI: 10.7717/PEERJ.9004
Abstract: Reverse Transcription-Quantitative PCR (RT-qPCR) is one of the standards for analytical measurement of different RNA species in biological models. However, current Reverse Transcription (RT) based priming strategies are unable to synthesize differing RNAs and ncRNAs especially miRNAs, within a single tube. We present a new methodology, referred to as RNAmp, that measures in parallel miRNA and mRNA expression. We demonstrate this in various cell lines, then evaluate clinical utility by quantifying several miRNAs and mRNA simultaneously in sera. PCR efficiency in RNAmp was estimated between 1.8 and 1.9 which is comparable to standard miRNA and random primer RT approaches. Furthermore, when using RNAmp to detect selected mRNA and miRNAs, the quantification cycle ( Cq ) was several cycles lower. This low volume single-tube duplex protocol reduces technical variation and reagent usage and is suitable for uniform analysis of single or multiple miRNAs and/or mRNAs within a single qPCR reaction.
Publisher: IEEE
Date: 08-2015
Publisher: IEEE
Date: 10-2019
Location: Australia
Location: United Kingdom of Great Britain and Northern Ireland
Start Date: 2010
End Date: 2012
Funder: University of Technology Sydney
View Funded ActivityStart Date: 2016
End Date: 2017
Funder: Cancer Research Institute
View Funded ActivityStart Date: 2021
End Date: 06-2024
Amount: $567,949.00
Funder: Australian Research Council
View Funded Activity