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.

Highlights

  • MiRNAs are a set of endogenous and small non-coding RNAs which induce degradation of target mRNAs or inhibit protein translation to control gene expression

  • Aberrant miRNA regulation would lead to a dynamic change in human protein-protein interaction network (PPIN), to activate or inhibit some signaling pathways related to diseases even cancers[6,7]

  • They compared the four important topological parameters, namely degree, betweenness centrality, clustering coefficient and closeness centrality of L0 proteins and L1 proteins jointly with random selected proteins, which revealed that miRNA-regulated targets and their interacting partners jointly show significantly higher connectivity and modularity than random selected proteins, even than direct targets alone. In their following work[12], they revealed that L0 proteins and L1 proteins together show a stronger functional relationship than L0 proteins alone. They further named the network formed by L0 proteins and L1 proteins the co-expressed protein-protein interaction network (CePPIN) which can be deemed as miRNA-regulated CePPIN

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Summary

Introduction

MiRNAs (microRNAs) are a set of endogenous and small non-coding RNAs which induce degradation of target mRNAs or inhibit protein translation to control gene expression. They compared the four important topological parameters, namely degree, betweenness centrality, clustering coefficient and closeness centrality of L0 proteins and L1 proteins jointly with random selected proteins, which revealed that miRNA-regulated targets and their interacting partners jointly show significantly higher connectivity and modularity than random selected proteins, even than direct targets alone In their following work[12], they revealed that L0 proteins and L1 proteins together show a stronger functional relationship than L0 proteins alone. Two representative miRNAs were selected, including miR-519d that regulates hepatocellular carcinoma only in our dataset and miR-21 that regulates 12 cancers including hepatocellular carcinoma in our dataset Their sub-network were constructed and functional analysis were implemented to stress our findings more concretely

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