MicroRNA-338-3p inhibits cell proliferation in hepatocellular carcinoma by target forkhead box P4 (FOXP4)

Int J Clin Exp Pathol. 2015 Jan 1;8(1):337-44. eCollection 2015.

Abstract

MicroRNAs (miRNAs) are a class of small, non-coding RNAs, which have demonstrated to important gene regulators, and have critical roles in diverse biological processes including cancer cell proliferation. Previous studies suggested microRNA-338-3p (miR-338-3p) was down-regulated and play tumor suppressor roles in gastric cancer, colorectal carcinoma and lung cancer. However, the role of miR-338-3p in hepatocellular carcinoma (HCC) is still unclear. In this study, we analyzed the expression of miR-338-3p in HCC tissues and HCC cell lines. We find that miR-338-3p was downregulated in HCC tissues and cell lines. Then functional studies demonstrate ectopic miR-338-3p expression significantly suppressed the in vitro proliferation and colony formation of HCC cells and cause to cell cycle arrest. Using bio-informatic method and report assay we identified a novel miR-338-3p target, FOXP4 in HCC cells. Furthermore, knockdown of FOXP4 have the similar effects in HCC corrected with miR-338-3p. These findings suggest that miR-338-3p regulates survival of HCC cells partially through the downregulation of FOXP4. Therefore, targeting with the miR-338-3p/FOXP4 axis might serve as a novel therapeutic application to treat HCC patients.

Keywords: FOXP4; HCC; cell cycle; cell growth; miR-338-3p.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Line, Tumor
  • Cell Proliferation* / genetics
  • Down-Regulation
  • Female
  • Forkhead Transcription Factors / genetics*
  • Forkhead Transcription Factors / metabolism
  • Gene Expression Regulation, Neoplastic / genetics*
  • Humans
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Male
  • MicroRNAs / genetics*
  • Middle Aged
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • FOXP4 protein, human
  • Forkhead Transcription Factors
  • MIRN338 microRNA, human
  • MicroRNAs