title: Down-regulation of miR-146a-5p and its potential targets in hepatocellular carcinoma validated by a TCGA- and GEO-based study.
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.
authors.affiliation: Department of Pathology First Affiliated Hospital of Guangxi Medical University Nanning China.
authors.forename: Xin
authors.identifier: 0000-0001-8561-6928
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Pathology First Affiliated Hospital of Guangxi Medical University Nanning China.
authors.forename: Zhi-Hua
authors.initials: ZH
authors.lastname: Ye
authors.affiliation: Department of Pathology First Affiliated Hospital of Guangxi Medical University Nanning China.
authors.forename: Hai-Wei
authors.initials: HW
authors.lastname: Liang
authors.affiliation: Department of Pathology First Affiliated Hospital of Guangxi Medical University Nanning China.
authors.forename: Fang-Hui
authors.initials: FH
authors.lastname: Ren
authors.affiliation: Department of Pathology First Affiliated Hospital of Guangxi Medical University Nanning China.
authors.forename: Ping
authors.initials: P
authors.lastname: Li
authors.affiliation: Department of Pathology First Affiliated Hospital of Guangxi Medical University Nanning China.
authors.forename: Yi-Wu
authors.initials: YW
authors.lastname: Dang
authors.affiliation: Department of Pathology First Affiliated Hospital of Guangxi Medical University Nanning China.
authors.forename: Gang
authors.initials: G
authors.lastname: Chen
keywords: HCC; expression; gene signature; hepatocellular carcinoma; miR‐146a‐5p; microRNA