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

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.