Journal Article•
Oncomirs : microRNAs with a role in cancer
TL;DR: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators as discussed by the authors, and have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
Abstract: I MicroRNAs (miRNAs) are an abundant class of small non-protein-coding RNAs that function as negative gene regulators. They regulate diverse biological processes, and bioinformatic data indicates that each miRNA can control hundreds of gene targets, underscoring the potential influence of miRNAs on almost every genetic pathway. Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes. miRNAs have been shown to repress the expression of important cancer-related genes and might prove useful in the diagnosis and treatment of cancer.
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TL;DR: Twenty state-of-the-art computational models of predicting miRNA-disease associations from different perspectives are reviewed, including five feasible and important research schemas, and future directions for further development of computational models are summarized.
Abstract: Circular RNAs (circRNAs) are a class of single-stranded, covalently closed RNA molecules with a variety of biological functions. Studies have shown that circRNAs are involved in a variety of biological processes and play an important role in the development of various complex diseases, so the identification of circRNA-disease associations would contribute to the diagnosis and treatment of diseases. In this review, we summarize the discovery, classifications and functions of circRNAs and introduce four important diseases associated with circRNAs. Then, we list some significant and publicly accessible databases containing comprehensive annotation resources of circRNAs and experimentally validated circRNA-disease associations. Next, we introduce some state-of-the-art computational models for predicting novel circRNA-disease associations and divide them into two categories, namely network algorithm-based and machine learning-based models. Subsequently, several evaluation methods of prediction performance of these computational models are summarized. Finally, we analyze the advantages and disadvantages of different types of computational models and provide some suggestions to promote the development of circRNA-disease association identification from the perspective of the construction of new computational models and the accumulation of circRNA-related data.
473 citations
TL;DR: This review summarizes: (i) the current understanding of interactions between miRNAs and their target genes, (ii) recent advances in the regulatory mechanisms that control the expression of genes related to carcinogenesis, and (iii) the role of mi RNAs in cancer diagnosis and therapy.
Abstract: In recent years, there has been a tremendous and growing interest among researchers to investigate the role of mircoRNA (miRNA) in normal cellular as well as in disease processes. miRNAs are a family of small non-coding RNAs which were reported to regulate the expression of various oncogenes or tumor suppressor genes. The expression profiling of miRNAs has already entered into cancer clinics as diagnostic and prognostic biomarkers to assess tumor initiation, progression and response to treatment in cancer patients. This review summarizes: (i) the current understanding of interactions between miRNAs and their target genes, (ii) recent advances in the regulatory mechanisms that control the expression of genes related to carcinogenesis, and (iii) the role of miRNAs in cancer diagnosis and therapy.
470 citations
TL;DR: Overexpression of pre-miR-206 reduced ERα and β-actin protein levels, with no effect on ERβ, E-cadherin, or glyceraldehyde-3-phosphate dehydrogenase.
Abstract: Micro-RNAs are small noncoding RNAs, which diminish the stability and/or translation of mRNAs. This study examined whether miR-206, previously shown to be elevated in estrogen receptor (ER)α-negative breast cancer, regulates the expression of ERα. Two putative miR-206 sites, (hERα1 and hERα2), were found in silico within the 3′-untranslated region of human ERα mRNA. Transfection of MCF-7 cells with pre-miR-206 or 2′-O-methyl antagomiR-206 specifically decreased or increased, respectively, ERα mRNA levels. Overexpression of pre-miR-206 reduced ERα and β-actin protein levels, with no effect on ERβ, E-cadherin, or glyceraldehyde-3-phosphate dehydrogenase. Reporter constructs containing the hERα1 or hERα2 binding sites inserted into the 3′-untranslated region of the luciferase mRNA conferred a 1.6- and 2.2-fold repression of luciferase activity, respectively, in HeLa cells. Both miR-206 sites responded accordingly to exogenous hsa-pre-miR-206 and 2′-O-methyl antagomiR-206, and both sites were rendered inactiv...
467 citations
TL;DR: It is reported that a fragile chromosomal region lost in specific hematopoietic malignancies, miR-203, functions as a tumor suppressor, and re-expression of this microRNA might have therapeutic benefits in specifichematopOieticmalignancies.
461 citations
TL;DR: It is suggested that HBV infection and activity of the TGF-β-miR-34a-CCL22 axis serve as potent etiological factors to predispose HCC patients for the development of PVTT, possibly through the creation of an immune-subversive microenvironment to favor colonization of disseminated HCC cells in the portal venous system.
460 citations
References
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TL;DR: Although they escaped notice until relatively recently, miRNAs comprise one of the more abundant classes of gene regulatory molecules in multicellular organisms and likely influence the output of many protein-coding genes.
32,946 citations
TL;DR: Two small lin-4 transcripts of approximately 22 and 61 nt were identified in C. elegans and found to contain sequences complementary to a repeated sequence element in the 3' untranslated region (UTR) of lin-14 mRNA, suggesting that lin- 4 regulates lin- 14 translation via an antisense RNA-RNA interaction.
11,932 citations
TL;DR: A new, bead-based flow cytometric miRNA expression profiling method is used to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers, and finds the miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours.
Abstract: Recent work has revealed the existence of a class of small non-coding RNA species, known as microRNAs (miRNAs), which have critical functions across various biological processes. Here we use a new, bead-based flow cytometric miRNA expression profiling method to present a systematic expression analysis of 217 mammalian miRNAs from 334 samples, including multiple human cancers. The miRNA profiles are surprisingly informative, reflecting the developmental lineage and differentiation state of the tumours. We observe a general downregulation of miRNAs in tumours compared with normal tissues. Furthermore, we were able to successfully classify poorly differentiated tumours using miRNA expression profiles, whereas messenger RNA profiles were highly inaccurate when applied to the same samples. These findings highlight the potential of miRNA profiling in cancer diagnosis.
9,470 citations
TL;DR: The predicted regulatory targets of mammalian miRNAs were enriched for genes involved in transcriptional regulation but also encompassed an unexpectedly broad range of other functions.
5,246 citations
TL;DR: The two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation.
Abstract: Hundreds of small RNAs of approximately 22 nucleotides, collectively named microRNAs (miRNAs), have been discovered recently in animals and plants. Although their functions are being unravelled, their mechanism of biogenesis remains poorly understood. miRNAs are transcribed as long primary transcripts (pri-miRNAs) whose maturation occurs through sequential processing events: the nuclear processing of the pri-miRNAs into stem-loop precursors of approximately 70 nucleotides (pre-miRNAs), and the cytoplasmic processing of pre-miRNAs into mature miRNAs. Dicer, a member of the RNase III superfamily of bidentate nucleases, mediates the latter step, whereas the processing enzyme for the former step is unknown. Here we identify another RNase III, human Drosha, as the core nuclease that executes the initiation step of miRNA processing in the nucleus. Immunopurified Drosha cleaved pri-miRNA to release pre-miRNA in vitro. Furthermore, RNA interference of Drosha resulted in the strong accumulation of pri-miRNA and the reduction of pre-miRNA and mature miRNA in vivo. Thus, the two RNase III proteins, Drosha and Dicer, may collaborate in the stepwise processing of miRNAs, and have key roles in miRNA-mediated gene regulation in processes such as development and differentiation.
5,191 citations