Oncomirs miRNA-221/222 and Tumor Suppressors miRNA-199a/195 Are Crucial miRNAs in Liver Cancer: A Systematic Analysis.

Abstract

BackgroundThe high mortality rate of hepatocellular carcinoma (HCC) is partly due to a lack of good diagnostic markers and treatment strategies. Recently, several microRNA (miRNA) profiling studies were conducted with HCC; however, their inconsistency means that their diagnostic or therapeutic value is debatable.AimsThis study aims to systematically evaluate the consistency of miRNAs from multiple independent studies.MethodsA systematic analysis of miRNAs from eligible publications was conducted, followed by real-time PCRs. The targets of highly consistent miRNAs were collected using online programs, followed by enrichment analyses for gene ontology terms and Kyoto encyclopedia of genes and genomes pathways.ResultsIn total, 241 differentially expressed miRNAs were reported in 13 HCC profiling studies, of which 137 were upregulated and 104 downregulated. Among consistently upregulated miRNAs (cutoff > fourfold), miRNA-222, miRNA-21, miRNA-221, miRNA-210, and miRNA-224 were found increased in 8, 6, 6, 5, and 5 different studies, respectively. Among 137 downregulated miRNAs, miRNA-195, miRNA-199a, miRNA-125b, and miRNA-99a were reported in 8, 8, 5, and 5 studies, respectively. These results were confirmed by real-time PCR. Enrichment analyses demonstrated that programmed cell death and proliferation play important roles during the interplay of miRNA with HCC.ConclusionsmiRNAs most consistently related to HCC are oncomirs miRNA-221/222 and tumor suppressors miRNA-199a/195.Electronic supplementary materialThe online version of this article (doi:10.1007/s10620-016-4156-8) contains supplementary material, which is available to authorized users.