MicroRNA-92a contributes to tumor growth of human hepatocellular carcinoma by targeting FBXW7

Oncol Rep. 2015 Nov;34(5):2576-84. doi: 10.3892/or.2015.4210. Epub 2015 Aug 19.

Abstract

Deregulation of microRNA-92a (miR-92a) has been reported in several human cancers and is associated with prognosis of patients. However, the clinical significance of miR-92a and the underlying mechanisms involved in hepatocarcinogenesis remain to be determined. The aim of the present study was to determine the role of miR-92a in hepatocellular carcinoma (HCC). The results showed that the expression of miR-92a was upregulated in HCC tissues as compared with matched tumor-adjacent tissues. A high expression of miR-92a was observed in HCC cell lines as compared with a non-transformed hepatic cell line. The gain- and loss-of-function studies revealed that miR-92a significantly promoted proliferation and cell cycle transition from G1 to S phase, and inhibited apoptosis of HCC cell in vitro. In tumor‑bearing nude mice, the downregulation of miR-92a suppressed tumor growth of HCC in vivo. miR-92a was inversely correlated with F-box and WD repeat domain-containing 7 (FBXW7) expression in HCC tissues. Furthermore, miR-92a negatively regulated FBXW7 abundance in HCC cells. In the present study, FBXW7 was identified as a direct target of miR-92a. Notably, alterations of FBXW7 expression abrogated the effects of miR-92a on HCC cell proliferation, cell cycle and apoptosis. Clinical association analysis revealed that a high expression of miR-92a was correlated with poor prognostic characteristics of HCC. Notably, the high expression of miR-92a conferred a reduced 5-year overall survival (OS) and recurrence-free survival (RFS) of HCC patients. The multivariate Cox regression analysis demonstrated that miR-92a expression was an independent prognostic marker for predicting survival of HCC patients. In conclusion, the results of the present study suggested that miR-92a promotes the tumor growth of HCC by targeting FBXW7 and may serve as a novel prognostic biomarker and therapeutic target for HCC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Hepatocellular / genetics*
  • Carcinoma, Hepatocellular / pathology*
  • Cell Cycle
  • Cell Cycle Proteins / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • F-Box Proteins / genetics*
  • F-Box-WD Repeat-Containing Protein 7
  • Female
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / genetics*
  • Liver Neoplasms / pathology*
  • Male
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Neoplasm Transplantation
  • Prognosis
  • Survival Analysis
  • Ubiquitin-Protein Ligases / genetics*
  • Up-Regulation

Substances

  • Cell Cycle Proteins
  • F-Box Proteins
  • F-Box-WD Repeat-Containing Protein 7
  • FBXW7 protein, human
  • MIRN92 microRNA, human
  • MicroRNAs
  • Ubiquitin-Protein Ligases