MicroRNAs in cancer
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Publication
Journal: Annual Review of Medicine
September/8/2009
Abstract
MicroRNAs (miRNAs) are small, noncoding RNAs with important functions in development, cell differentiation, and regulation of cell cycle and apoptosis. MiRNA expression is deregulated in cancer by a variety of mechanisms including amplification, deletion, mutation, and epigenetic silencing. Several studies have now shown that miRNAs are involved in the initiation and progression of cancer. In this review, we briefly describe miRNA biogenesis and discuss how miRNAs can act as oncogenes and tumor suppressors. We also address the role of miRNAs in the diagnosis, prognosis, and treatment of cancer.
Publication
Journal: EMBO Molecular Medicine
July/15/2012
Abstract
Early studies have shown how aberrantly expressed microRNAs are a hallmark of several diseases like cancer. MicroRNA expression profiling was shown to be associated with tumour development, progression and response to therapy, suggesting their possible use as diagnostic, prognostic and predictive biomarkers. Moreover, based on the increasing number of studies demonstrating that microRNAs can function as potential oncogenes or oncosuppressor genes, with the goal to improve disease response and increase cure rates, miRNA-based anticancer therapies have recently been exploited, either alone or in combination with current targeted therapies. The advantage of using microRNA approaches is based on its ability to concurrently target multiple effectors of pathways involved in cell differentiation, proliferation and survival. Here, we review our current knowledge about the involvement of microRNAs in cancer, and their potential as diagnostic, prognostic and therapeutic tools.
Publication
Journal: Annual Review of Pathology: Mechanisms of Disease
May/27/2009
Abstract
Within the past few years, studies on microRNA (miRNA) and cancer have burst onto the scene. Profiling of the miRNome (global miRNA expression levels) has become prevalent, and abundant miRNome data are currently available for various cancers. The pattern of miRNA expression can be correlated with cancer type, stage, and other clinical variables, so miRNA profiling can be used as a tool for cancer diagnosis and prognosis. miRNA expression analyses also suggest oncogenic (or tumor-suppressive) roles of miRNAs. miRNAs play roles in almost all aspects of cancer biology, such as proliferation, apoptosis, invasion/metastasis, and angiogenesis. Given that many miRNAs are deregulated in cancers but have not yet been further studied, it is expected that more miRNAs will emerge as players in the etiology and progression of cancer. Here we also discuss miRNAs as a tool for cancer therapy.
Publication
Journal: Physiological Reviews
September/5/2011
Abstract
MicroRNAs (miRNAs) are a class of posttranscriptional regulators that have recently introduced an additional level of intricacy to our understanding of gene regulation. There are currently over 10,000 miRNAs that have been identified in a range of species including metazoa, mycetozoa, viridiplantae, and viruses, of which 940, to date, are found in humans. It is estimated that more than 60% of human protein-coding genes harbor miRNA target sites in their 3' untranslated region and, thus, are potentially regulated by these molecules in health and disease. This review will first briefly describe the discovery, structure, and mode of function of miRNAs in mammalian cells, before elaborating on their roles and significance during development and pathogenesis in the various mammalian organs, while attempting to reconcile their functions with our existing knowledge of their targets. Finally, we will summarize some of the advances made in utilizing miRNAs in therapeutics.
Publication
Journal: Gastroenterology
September/30/2012
Abstract
The incidence of gastroesophageal cancers is increasing each year, but despite much research, their molecular mechanisms are incompletely understood. microRNAs (miRNAs) are noncoding RNAs that have been associated with gastroesophageal carcinogenesis. We review the involvement of miRNAs in gastric and esophageal cancers and their mechanisms of regulation, effects on gene expression, and biological functions. Many miRNAs are dysregulated in gastroesophageal cancer cells via alterations in transcription, epigenetic features, or copy number of the genes that encode them. Each type of gastroesophageal tumor has a unique gene expression profile. miRNAs contribute to gastroesophageal carcinogenesis by altering expression of oncogenes and tumor suppressors to affect cell proliferation, apoptosis, and motility and invasion. A number of miRNAs, including circulating miRNAs, have been associated with tumor type or stage, or patient survival, and might be developed as diagnostic or prognostic markers. Greater understanding of the roles of miRNAs in gastroesophageal carcinogenesis could provide insights into the mechanisms of tumor development and identify therapeutic targets.
Publication
Journal: European Journal of Cancer
November/17/2011
Abstract
MicroRNAs (miRNAs) are small, non-coding, endogenous RNAs that regulate gene expression at the post-transcriptional level. MiRNAs play important roles in regulating a variety of biological process such as proliferation, differentiation and apoptosis. It has been demonstrated that miRNAs have a crucial function in oncogenesis by regulating cell proliferation and apoptosis as oncogenes or tumour suppressors. As several reports have underlined the possible contribution of miRNAs to promote or evade apoptosis, it seems that the dysregulation of miRNAs involved in apoptosis may provide a mechanism for cancer development. Given emerging evidence that points to oncogenic and tumour suppressive roles of miRNAs in cancer and apoptosis, it is thought that manipulating miRNA expression level may be a potential therapeutic strategy for curing cancer.
Publication
Journal: Journal of Biomedical Science
April/2/2013
Abstract
MicroRNAs (miRNAs) are involved in multiple biological activities as well as disease progression including cancer. Interestingly, miRNAs could act as either tumor suppressors or oncogenes depending on the functions of their targets. Using high-throughput profiling, dysregulation of miRNAs has been widely observed in different stages of cancer, and there is mounting evidence demonstrating several misguided mechanisms that cause miRNA dysregulation. In this review, we summarize the key functions of miRNAs in cancer, especially those affecting tumor metastasis and drug resistance. Moreover, the mechanisms leading to dysregulation of miRNAs, including genomic abnormalities, DNA/histone modifications, transcriptional regulation, abnormal biogenesis, and interaction between miRNAs, are also discussed.
Publication
Journal: Nature Reviews Gastroenterology and Hepatology
August/29/2013
Abstract
Cancers of the oesophagus, gastro-oesophageal junction and stomach (upper gastrointestinal tract cancers; UGICs) pose a major health risk around the world. Collectively, the 5-year survival rate has remained <15%, and therapeutic improvements have been very slow and small. Novel molecules for early diagnosis, prognosis and therapy are, therefore, urgently needed. The role that microRNA (miRNA) molecules have in UGICs are worth pursuing to this end. miRNAs are small noncoding RNA molecules that regulate ∼60% of coding genes in humans and, therefore, are pivotal in mediating and regulating many physiologic processes. miRNAs are deregulated in many disease states, particularly in cancer, making them important targets. Here, we review the growing body of evidence regarding the alterations of miRNAs in UGICs. By suppressing translation and/or promoting degradation of mRNAs, miRNAs can contribute to carcinogenesis and progression of UGICs. In-depth studies of miRNAs in UGICs might yield novel insights and potential novel therapeutic strategies.
Publication
Journal: Biochimica et Biophysica Acta - General Subjects
March/28/2012
Abstract
The hepatitis B virus (HBV) is a widespread human pathogen and chronic HBV infection is a major risk factor for hepatocellular carcinoma (HCC). The role of microRNA (miRNA) in the replication and pathogenesis was reviewed. So far none of HBV-encoded miRNA has been identified. Cellular miRNAs have shown able to regulate HBV at the transcription level either by targeting to cellular transcriptions factors required for HBV gene expression, or by a directly binding to HBV transcripts. We also summarized the changed patterns of cellular miRNAs from hepatitis B progressing to cirrhosis and then liver cancer. The changing of a few of miRNAs, such as miR-122 or miR-21, were reproduced and worthy of further research by a deep sequencing and functional validation. These HBV-specific miRNAs should potentially become biomarkers for HBV infection and HBV-positive HCC diagnosis. The understanding of miRNA biology paved the way for applying miRNAs-based RNAi against HBV replication with minimal toxicities. This article is part of a Special Issue entitled: MicroRNAs in viral gene regulation.
Publication
Journal: Cellular and Molecular Life Sciences
December/27/2012
Abstract
The emerging role of microRNAs (miRNAs) in the epigenetic regulation of many cellular processes has become recognized in both basic research and translational medicine as an important way that gene expression can be fine-tuned. Breast cancer is the most frequent cancer in women, with about one million new cases diagnosed each year worldwide. Starting with the early work of miRNA profiling, more effort has now been put on functions of miRNAs in normal mammary stem cells, breast cancer initiating cells and metastatic cells, and therapy-resistant cancer cells. Future translational studies may focus on identifying miRNA signatures as cancer biomarkers and developing miRNA-based targeted therapeutics.
Publication
Journal: Current Opinion in Pharmacology
February/7/2010
Abstract
The molecular genetics of Barrett's esophagus (BE) and its evolution to esophageal adenocarcinoma (EAC) have been widely studied; however, the molecular mechanism of BE-EAC carcinogenesis has not been completely understood. MicroRNA (miRNA) is now essential to understand the molecular mechanism of cancer progression. Recent findings include the following: firstly, miRNA expression profiles can distinguish between BE and EAC; secondly, miR-196a is upregulated in EAC tissues targeting annexin A1, thereby exerting antiapoptotic effects and contributing to EAC cell survival; miR-196a may also constitute a good biomarker of progression during BE-EAC carcinogenesis; and thirdly, The miR-106b-25 polycistron is activated by genomic amplification and is involved in esophageal neoplastic progression and proliferation via the suppression of two target genes, p21 and Bim.
Publication
Journal: Journal of Cellular and Molecular Medicine
February/16/2011
Abstract
Epithelial ovarian cancer (EOC) has the highest mortality rate of all gynaecological cancers. One of the greatest impediments to improving outcome is an incomplete understanding of the molecular underpinnings of EOC pathogenesis and progression. Recent studies suggest that microRNAs (miRNAs) are involved in ovarian tumorigenesis and cancer development. Several miRNA profiling studies have identified some consensus aberrantly expressed miRNAs in EOC tissues, and these EOC-related miRNAs may play critical roles in the pathogenesis and progression of EOC. Moreover, some of the miRNAs may have diagnostic or prognostic significance. In this review, recent progress to reveal the role of miRNAs in EOC will be addressed, and a model for miRNA functions in ovarian cancer initiation and progression will be proposed.
Publication
Journal: Frontiers in Genetics
October/23/2012
Abstract
MicroRNAs (miRNAs) play an important role in various physiologic and developmental processes and in the initiation and progression of cancer. This class of small, non-coding RNAs critically regulate gene expression at the post-transcriptional level and evidence suggests that they may function as both oncogenes and tumor suppressors. Colorectal cancer (CRC) is a major healthcare concern worldwide and in order to reduce CRC related deaths, research is aimed into the search for some novel screening approaches. In this sense, miRNAs are rapidly emerging as a novel class of biomarkers, with good potential as diagnostic and therapeutic targets. This review summarizes the recent findings of the clinicopathological relevance that miRNAs have in CRC initiation, development, and progress, highlighting their potential diagnostic, prognostic, and therapeutic use in CRC, focusing on the group of microsatellite instable and the group of hypermethylated CRCs, as well as discussing future prospects.
Publication
Journal: Pharmaceutical Research
August/16/2010
Abstract
MicroRNAs (miRNAs) constitute an evolutionarily conserved class of small non-coding RNAs that are endogenously expressed with crucial functions in fundamental cellular processes such as cell cycle, apoptosis and differentiation. Disturbance of miRNA expression and function leads to deregulation of basic cellular processes leading to tumorigenesis. A growing body of experimental evidence suggests that human tumors have deregulated expression of microRNAs, which have been proposed as novel oncogenes or tumor suppressors. Recent studies have shown that microRNA expression patterns serve as phenotypic signatures of different cancers and could be used as diagnostic, prognostic and therapeutic tools. A few studies have analyzed global microRNA expression profiles or the functional role of microRNAs in prostate cancer. Here we have reviewed the role of microRNAs in prostate carcinogenesis by summarizing the findings from such studies. In addition, recent evidence indicates that dietary factors play an important role in the process of carcinogenesis through modulation of miRNA expression, though such studies are lacking in regards to prostate cancer. It has been proposed that dietary modulation of miRNA expression may contribute to the cancer-protective effects of dietary components. In this review, we have summarized findings from studies on the effect of dietary agents on miRNA expression and function.
Publication
Journal: World Journal of Gastroenterology
April/4/2010
Abstract
Barrett's esophagus is a premalignant condition caused by gastroesophageal reflux. Once developed, it can progress through varying grades of dysplasia to esophageal adenocarcinoma. Whilst it is well accepted that Barrett's esophagus is caused by gastroesophageal reflux, the molecular mechanisms of its pathogenesis and progression to cancer remain unclear. MicroRNAs (miRNAs) are short segments of RNA that have been shown to control the expression of many human genes. They have been implicated in most cellular processes, and the role of miRNAs in disease development is becoming increasingly evident. Understanding altered miRNA expression is likely to help unravel the molecular mechanisms that underpin the development of Barrett's esophagus and its progression to cancer.
Publication
Journal: Experimental Biology and Medicine
May/6/2012
Abstract
MicroRNAs (miRNAs) are short non-protein-coding RNAs that post-transcriptionally regulate mRNA expression. A large body of evidence has identified important roles for these regulators in cell proliferation, differentiation, apoptosis and metabolism, as well as activation of oncogenic and antioncogenic signals. Aberrant expression of miRNAs has been found in most human malignancies and is strongly associated with tumorigenesis, prediction, diagnosis, progress, treatment and prognosis. Thus, miRNAs may become an intriguing and promising therapeutic target for many diseases, including cancer. In addition, research into miRNAs may provide insight into the mechanisms underlying tumor occurrence, progression and metastasis. This review summarizes the current knowledge of miRNAs, their roles in lung cancer and avenues for future research.
Publication
Journal: Frontiers in Genetics
January/14/2013
Abstract
MicroRNAs (miRNAs) are small, non-coding RNAs that post-transcriptionally regulate gene expression. Their altered expression and functional activity have been observed in many human cancers. miRNAs represent promising diagnostic and prognostic molecular biomarkers, and also serve as novel therapeutic targets. We performed a systematic analysis of scientific reports that link differences in miRNA expression with the pathogenesis of bladder cancer (BC). This literature review is the first comprehensive database of miRNA molecules with biased expression profiles in BC. Among the 95 differentially expressed miRNAs that we identified from the literature, we classify 48 as up-regulated in BC, 35 as down-regulated, and 12 as contradictory (contradictory data were reported in one or more studies on the gene). In addition, we discuss the possible roles of differentially expressed miRNAs in the regulation of intracellular signaling pathways in BC.
Publication
Journal: Chinese journal of cancer
January/30/2013
Abstract
Naturally occurring microRNAs (miRNAs), small non-coding RNAs of 19 to 24 nucleotides (nt), are encoded in the genomes of invertebrates, vertebrates, and plants. miRNAs act as regulators of gene expression during development and differentiation at the transcriptional, posttranscriptional, and/or translational levels, although most target genes are still elusive. Many miRNAs are conserved in sequence between distantly related organisms, suggesting that these molecules participate in essential processes. In this review, we present principles related to the basic and translational research that has emerged in the last decade, a period that can be truly considered the "miRNA revolution" in molecular oncology. These principles include the regulation mechanism of miRNA expression, functions of miRNAs in cancers, diagnostic values and therapeutic potentials of miRNAs. Furthermore, we present a compendium of information about the main miRNAs that have been identified in the last several years as playing important roles in cancers. Also, we orient the reader to several additional reviews that may provide a deeper understanding of this new and exciting field of research.
Publication
Journal: The Netherlands journal of medicine
December/15/2013
Abstract
Oesophageal cancer is a common cancer worldwide with a very poor prognosis. Oesophageal squamous cell carcinoma (OSCC) is the major subtype of oesophageal cancer but also one of the least studied cancers worldwide. Although the molecular genetics of OSCC have been widely studied, the molecular mechanism of OSCC carcinogenesis is not completely understood. MicroRNA (miRNA) is now essential to understanding the molecular mechanism of cancer progression. Recent findings include the following: 1) recent findings regarding the functions of miRNA; 2) some of the latest findings on expression profile of miRNA involved in OSCC; 3) miRNAs and their target genes and molecular mechanisms in OSCC; and 4) the therapeutic-clinical potential of miRNAs in OSCC. We can make full use of this knowledge to guide us to evaluate and improve the patient's condition and choose the most fitting medical treatment or explore new approaches to improve the survival ratio of OSCC patients.