Dissecting the regulation rules of cancer-related miRNAs based on network analysis

Abstract

miRNAs (microRNAs) are a set of endogenous and small non-coding RNAs which specifically induce degradation of target mRNAs or inhibit protein translation to control gene expression. Obviously, aberrant miRNA expression in human cells will lead to a serious of changes in protein-protein interaction network (PPIN), thus to activate or inactivate some pathways related to various diseases, especially carcinogenesis. In this study, we systematically constructed the miRNA-regulated co-expressed protein-protein interaction network (CePPIN) for 17 cancers firstly. We investigated the topological parameters and functional annotation for the proteins in CePPIN, especially for those miRNA targets. We found that targets regulated by more miRNAs tend to play a more important role in the forming process of cancers. We further elucidated the miRNA regulation rules in PPIN from a more systematical perspective. By GO and KEGG pathway analysis, miRNA targets are involved in various cellular processes mostly related to cell cycle, such as cell proliferation, growth, differentiation, etc. Through the Pfam classification, we found that miRNAs belonging to the same family tend to have targets from the same family which displays the synergistic function of these miRNAs. Finally, the case study on miR-519d and miR-21-regulated sub-network was performed to support our findings.

Targeting genes and signaling pathways of transcriptional suppressor ZHX2 in hepatocellular carcinoma: a Chromatin Immunoprecipitation-sequencing (ChIP-seq) investigation

“…The Gene Ontology database (gene ontology, GO) (http://www.geneontology.org/) was used for the classification and functional analysis of genes with ZHX2 binding sites [17][18][19][20][21][22]. Genes with ZHX2 binding sites were used for pathway enrichment analyses based on the Kyoto Encyclopedia of Genes and Genomes (KEGG, http://www.genome.jp) [20,[23][24][25][26][27][28][29]. A p<0.05 was set as the threshold value of significant gene enrichment.…”

MicroRNAs tend to synergistically control expression of genes encoding extensively-expressed proteins in humans

“…One miRNA usually physically interacts with hundreds of target genes ( Zhou & Yang, 2012 ), suggesting the advantage of high-throughput and integrative gene regulation ( Liu et al, 2016 ). However, it was also proposed that an inherent deficiency should be not ignored regarding the operation of a ‘one to many’ system like this.…”

Correlation between miR-200 Family Overexpression and Cancer Prognosis

“…miRNAs are small noncoding RNAs that regulate human protein-coding gene expression of specific mRNAs by either translational repression or degradation. miRNA expression signatures have distinct functions in controlling the cell cycle, proliferation, invasion, and metastasis [ 41 ], which could thus be developed into a potential prognostic signature [ 42 ]. The latest miRBase release contains 24,521 miRNA loci from 206 species, further processed to produce 30,424 mature miRNA products [ 43 ].…”