Down-regulation of miR-146a-5p and its potential targets in hepatocellular carcinoma validated by a TCGA- and GEO-based study

Xin Zhang, Zhi Hua Ye, Hai Wei Liang, Fang Hui Ren, Ping Li, Yi Wu Dang, Gang Chen

Research output: Contribution to journalArticlepeer-review

33 Citations (Scopus)

Abstract

Our previous research has demonstrated that miR-146a-5p is down-regulated in hepatocellular carcinoma (HCC) and might play a tumor-suppressive role. In this study, we sought to validate the decreased expression with a larger cohort and to explore potential molecular mechanisms. GEO and TCGA databases were used to gather miR-146a-5p expression data in HCC, which included 762 HCC and 454 noncancerous liver tissues. A meta-analysis of the GEO-based microarrays, TCGA-based RNA-seq data, and additional qRT-PCR data validated the down-regulation of miR-146a-5p in HCC and no publication bias was observed. Integrated genes were generated by overlapping miR-146a-5p-related genes from predicted and formerly reported HCC-related genes using natural language processing. The overlaps were comprehensively analyzed to discover the potential gene signatures, regulatory pathways, and networks of miR-146a-5p in HCC. A total of 251 miR-146a-5p potential target genes were predicted by bioinformatics platforms and 104 genes were considered as both HCC- and miR-146a-5p-related overlaps. RAC1 was the most connected hub gene for miR-146a-5p and four pathways with high enrichment (VEGF signaling pathway, adherens junction, toll-like receptor signaling pathway, and neurotrophin signaling pathway) were denoted for the overlapped genes. The down-regulation of miR-146a-5p in HCC has been validated with the most complete data possible. The potential gene signatures, regulatory pathways, and networks identified for miR-146a-5p in HCC could prove useful for molecular-targeted diagnostics and therapeutics.

Original languageEnglish
Pages (from-to)504-521
Number of pages18
JournalFebs Open Bio
Volume7
Issue number4
DOIs
Publication statusPublished - 1 Apr 2017
Externally publishedYes

Keywords

  • expression
  • gene signature
  • HCC
  • hepatocellular carcinoma
  • microRNA
  • miR-146a-5p

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