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CRISPR Gene Editing Tool for MicroRNA Cluster Network Analysis
Published on: April 25, 2022
Dissecting the regulation rules of cancer-related miRNAs based on network analysis
Zhongyu Liu1, Yanzhi Guo2, Xuemei Pu2
1College of Life Science, Sichuan University, Chengdu, Sichuan 610064, PR China.
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.
Insights
MicroRNAs (miRNAs) regulate gene expression by targeting mRNAs. Aberrant miRNA activity in cancer highlights their role in disease, with more targeted miRNAs playing key roles in cancer development.
Area of Science:
- Genomics
- Molecular Biology
- Bioinformatics
Background:
- MicroRNAs (miRNAs) are small non-coding RNAs that regulate gene expression by degrading target mRNAs or inhibiting protein translation.
- Aberrant miRNA expression is linked to various diseases, particularly cancer, by altering protein-protein interaction networks (PPINs).
Purpose of the Study:
- To systematically construct and analyze the miRNA-regulated co-expressed protein-protein interaction network (CePPIN) for 17 human cancers.
- To investigate the role of miRNA targets in cancer development and elucidate miRNA regulation rules within PPINs.
Main Methods:
- Construction of miRNA-CePPIN for 17 cancers.
- Analysis of topological parameters and functional annotation of proteins within CePPIN.
- Gene Ontology (GO) and KEGG pathway analysis.
- Pfam classification.
- Case study on specific miRNA-regulated subnetworks.
Main Results:
- Proteins targeted by multiple miRNAs play significant roles in cancer formation.
- miRNA targets are predominantly involved in cell cycle-related processes like proliferation and differentiation.
- miRNAs from the same family often target proteins from the same family, indicating synergistic functions.
Conclusions:
- The study provides a systematic understanding of miRNA regulation in cancer PPINs.
- Findings highlight the critical role of miRNA-target interactions in cellular processes relevant to carcinogenesis.
- The identified miRNA regulation rules and targets offer insights into potential cancer therapies.
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