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

Dig Dis Sci. 2016 Aug;61(8):2315-2327. doi: 10.1007/s10620-016-4156-8. Epub 2016 May 7.

Abstract

Background: The 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.

Aims: This study aims to systematically evaluate the consistency of miRNAs from multiple independent studies.

Methods: A 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.

Results: In 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.

Conclusions: miRNAs most consistently related to HCC are oncomirs miRNA-221/222 and tumor suppressors miRNA-199a/195.

Keywords: Differential expression; Hepatocellular carcinoma; Systematic study; miRNA.

Publication types

  • Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / genetics*
  • Carcinoma, Hepatocellular / genetics*
  • Cell Proliferation / genetics*
  • Humans
  • Liver Neoplasms / genetics*
  • MicroRNAs / genetics*

Substances

  • MIRN195 microRNA, human
  • MIRN21 microRNA, human
  • MIRN221 microRNA, human
  • MIRN222 microRNA, human
  • MIRN224 microRNA, human
  • MIRN99 microRNA, human
  • MicroRNAs
  • mirn199 microRNA, human