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Epigenetic regulation of microRNAs in a hepatocellular carcinoma cell line

ABSTRACT: Emerging evidence indicates that microRNAs (miRNAs) are often deregulated in hepatocellular carcinoma (HCC) and that some specific miRNAs are associated with the initiation and progression of HCC. Although miRNAs plays important roles in HCC tumor formation, little is known about the mechanisms that control miRNA expression in HCC. To test if miRNA genes are targeted by epigenetic modifications, miRNA expression profiling was performed in the HCC cell line SK-HEP-1 treated or untreated with 5-AzaC (DNA hypomethylating agent). The results showed that the expression of 33 miRNAs was regulated by the epigenetic drugs. Considering the functional importance of miRNAs in tumorigenesis, it is clear that additional layers of control by miRNA function linked to the epigenetic regulators may exist during cancer development.

ORGANISM(S): Homo sapiens

PROVIDER: GSE31026 | GEO | 2022/10/05

REPOSITORIES: GEO

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Project description:Schmitz2014 - RNA triplex formation The model is parameterized using the parameters for gene CCDC3 from Supplementary Table S1. The two miRNAs which form the triplex together with CCDC3 are miR-551b and miR-138. This model is described in the article: Cooperative gene regulation by microRNA pairs and their identification using a computational workflow. Schmitz U, Lai X, Winter F, Wolkenhauer O, Vera J, Gupta SK. Nucleic Acids Res. 2014 Jul; 42(12): 7539-7552 Abstract: MicroRNAs (miRNAs) are an integral part of gene regulation at the post-transcriptional level. Recently, it has been shown that pairs of miRNAs can repress the translation of a target mRNA in a cooperative manner, which leads to an enhanced effectiveness and specificity in target repression. However, it remains unclear which miRNA pairs can synergize and which genes are target of cooperative miRNA regulation. In this paper, we present a computational workflow for the prediction and analysis of cooperating miRNAs and their mutual target genes, which we refer to as RNA triplexes. The workflow integrates methods of miRNA target prediction; triplex structure analysis; molecular dynamics simulations and mathematical modeling for a reliable prediction of functional RNA triplexes and target repression efficiency. In a case study we analyzed the human genome and identified several thousand targets of cooperative gene regulation. Our results suggest that miRNA cooperativity is a frequent mechanism for an enhanced target repression by pairs of miRNAs facilitating distinctive and fine-tuned target gene expression patterns. Human RNA triplexes predicted and characterized in this study are organized in a web resource at www.sbi.uni-rostock.de/triplexrna/. This model is hosted on BioModels Database and identified by: BIOMD0000000530. To cite BioModels Database, please use: BioModels Database: An enhanced, curated and annotated resource for published quantitative kinetic models. To the extent possible under law, all copyright and related or neighbouring rights to this encoded model have been dedicated to the public domain worldwide. Please refer to CC0 Public Domain Dedication for more information.

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Epigenetic regulation of microRNAs in a hepatocellular carcinoma cell line

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