Overexpression of E2F mRNAs associated with gastric cancer progression identified by the transcription factor and miRNA co-regulatory network analysis

PLoS One. 2015 Feb 3;10(2):e0116979. doi: 10.1371/journal.pone.0116979. eCollection 2015.

Abstract

Gene expression is regulated at the transcription and translation levels; thus, both transcription factors (TFs) and microRNAs (miRNA) play roles in regulation of gene expression. This study profiled differentially expressed mRNAs and miRNAs in gastric cancer tissues to construct a TF and miRNA co-regulatory network in order to identify altered genes in gastric cancer progression. A total of 70 cases gastric cancer and paired adjacent normal tissues were subjected to cDNA and miRNA microarray analyses. We obtained 887 up-regulated and 93 down-regulated genes and 41 down-regulated and 4 up-regulated miRNAs in gastric cancer tissues. Using the Transcriptional Regulatory Element Database, we obtained 105 genes that are regulated by the E2F family of genes and using Targetscan, miRanda, miRDB and miRWalk tools, we predicted potential targeting genes of these 45 miRNAs. We then built up the E2F-related TF and miRNA co-regulatory gene network and identified 9 hub-genes. Furthermore, we found that levels of E2F1, 2, 3, 4, 5, and 7 mRNAs associated with gastric cancer cell invasion capacity, and has associated with tumor differentiation. These data showed Overexpression of E2F mRNAs associated with gastric cancer progression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Computational Biology*
  • Disease Progression*
  • E2F Transcription Factors / genetics*
  • Female
  • Gene Expression Regulation, Neoplastic*
  • Gene Regulatory Networks*
  • Humans
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Stomach Neoplasms / genetics*
  • Stomach Neoplasms / pathology

Substances

  • E2F Transcription Factors
  • MicroRNAs
  • RNA, Messenger

Associated data

  • GEO/GSE63089

Grants and funding

This work was supported in part by grants from National Natural Science Foundation of China (#81320108025 and #81472662), Foundation of Jilin Province Science and Technology Department (#20130522013JH and #20140414048GH) and the Norman Bethune Program of Jilin University (#2012219). The authors also thank the Medjaden Bioscience Limited (Hong Kong, China) for editing and proofreading this manuscript. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.