MiR-199a regulates cell proliferation and survival by targeting FZD7

PLoS One. 2014 Oct 14;9(10):e110074. doi: 10.1371/journal.pone.0110074. eCollection 2014.

Abstract

A growing amount of evidence indicates that miRNAs are important regulators of multiple cellular processes and, when expressed aberrantly in different types of cancer such as hepatocellular carcinoma (HCC), play significant roles in tumorigenesis and progression. Aberrant expression of miR-199a-5p (also called miR-199a) was found to contribute to carcinogenesis in different types of cancer, including HCC. However, the precise molecular mechanism is not yet fully understood. The present study showed that miR-199a is frequently down-regulated in HCC tissues and cells. Importantly, lower expression of miR-199a was significantly correlated with the malignant potential and poor prognosis of HCC, and restoration of miR-199a in HCC cells led to inhibition of the cell proliferation and cell cycle in vitro and in vivo. Furthermore, Frizzled type 7 receptor (FZD7), the most important Wnt receptor involved in cancer development and progression, was identified as a functional target of miR-199a. In addition, these findings were further strengthened by results showing that expression of FZD7 was inversely correlated with miR-199a in both HCC tissues and cells and that over-expression of miR-199a could significantly down-regulate the expression of genes downstream of FZD7, including β-catenin, Jun, Cyclin D1 and Myc. In conclusion, these findings not only help us to better elucidate the molecular mechanisms of hepatocarcinogenesis from a fresh perspective but also provide a new theoretical basis to further investigate miR-199a as a potential biomarker and a promising approach for HCC treatment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Binding Sites
  • Carcinoma, Hepatocellular / genetics
  • Carcinoma, Hepatocellular / metabolism*
  • Carcinoma, Hepatocellular / mortality
  • Cell Proliferation*
  • Cell Survival*
  • Female
  • Frizzled Receptors / genetics*
  • Frizzled Receptors / metabolism
  • Gene Expression
  • Gene Expression Regulation, Neoplastic
  • Hep G2 Cells
  • Humans
  • Kaplan-Meier Estimate
  • Liver Neoplasms / genetics
  • Liver Neoplasms / metabolism*
  • Liver Neoplasms / mortality
  • Male
  • MicroRNAs / physiology*
  • Middle Aged
  • RNA Interference

Substances

  • FZD7 protein, human
  • Frizzled Receptors
  • MicroRNAs
  • mirn199 microRNA, human

Grants and funding

This work was supported by grant 81101852 from the National Natural Science Foundation of China (http://www.nsfc.gov.cn/). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.