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Functional dissection of human targets for KSHV-encoded miRNAs using network analysis.

Yu Wang1, Yun Lin2, Yanzhi Guo3

  • 1College of Chemistry, Sichuan University, Chengdu, 610064, P.R. China.

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|June 11, 2017
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Summary

Kaposi's sarcoma-associated herpesvirus (KSHV) encodes microRNAs (miRNAs) that target host genes, influencing viral pathogenesis. These targets often act as network hubs involved in immune regulation and cell cycle, contributing to disease or viral survival.

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Area of Science:

  • Virology
  • Bioinformatics
  • Network Biology

Background:

  • Kaposi's sarcoma-associated herpesvirus (KSHV) causes significant diseases like Kaposi's sarcoma.
  • Understanding KSHV's pathogenesis requires insights into its microRNA (miRNA) regulatory mechanisms.

Purpose of the Study:

  • To construct and analyze the KSHV-encoded miRNA-regulated co-expressed protein-protein interaction network (CePPIN).
  • To elucidate the roles of KSHV miRNAs in viral pathogenesis by examining their target genes within the network.

Main Methods:

  • Systematic construction of the KSHV CePPIN.
  • Analysis of topological parameters for proteins, particularly miRNA targets.
  • Gene Ontology (GO) and KEGG pathway analysis of miRNA targets.
  • Enrichment analysis to identify functional modules.
  • Comparative analysis of common and specific miRNA targets.

Main Results:

  • KSHV miRNA targets are identified as hubs and bottlenecks in the CePPIN.
  • miRNA targets are significantly enriched in immune regulation and cell cycle pathways.
  • Six key functional modules related to KSHV pathogenesis were identified.
  • Common and specific targets exhibit distinct topological properties and functions.

Conclusions:

  • KSHV miRNAs play dual roles: mimicking oncogenic human miRNAs to promote tumorigenesis and aiding viral survival.
  • The CePPIN provides a framework for understanding miRNA-mediated KSHV pathogenesis.
  • Target gene analysis reveals distinct functional categories for KSHV miRNAs.