MicroRNA-493 suppresses tumor growth, invasion and metastasis of lung cancer by regulating E2F1

PLoS One. 2014 Aug 8;9(8):e102602. doi: 10.1371/journal.pone.0102602. eCollection 2014.

Abstract

miRNAs have been proposed to be key regulators of progression and metastasis in cancer. However, an understanding of their roles and molecular mechanisms is needed to provide deeper insights for better therapeutic opportunities. In this study we investigated the role and mechanism of miR-493 in the development and progression of nonsmall-cell lung cancer (NSCLC). Our data indicated that the expression of miR-493 was markedly reduced in pulmonary carcinoma. The ectopic expression of miR-493 impaired cell growth and invasion in vitro and in vivo. Mechanically, miR-493 commonly directly targeted E2F1, which resulted in a robust reduction of the expression of mRNA and protein. This effect, in turn, decreased the growth, invasion and metastasis of lung cancer cells. Our findings highlight the importance of miR-493 dysfunction in promoting tumor progression, and implicate miR-493 as a potential therapeutic target in lung cancer.

Publication types

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

MeSH terms

  • Analysis of Variance
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Cell Movement / genetics
  • Cell Movement / physiology
  • Cell Proliferation / genetics
  • Cell Proliferation / physiology
  • DNA Primers / genetics
  • Disease Progression
  • E2F1 Transcription Factor / genetics
  • E2F1 Transcription Factor / metabolism*
  • Flow Cytometry
  • Gene Expression Regulation, Neoplastic / genetics*
  • Gene Silencing
  • Humans
  • Immunohistochemistry
  • Luciferases
  • MicroRNAs / metabolism*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / physiopathology*
  • Neoplasm Metastasis / genetics
  • Neoplasm Metastasis / physiopathology*
  • Real-Time Polymerase Chain Reaction
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / physiology

Substances

  • DNA Primers
  • E2F1 Transcription Factor
  • E2F1 protein, human
  • MIRN493 microRNA, human
  • MicroRNAs
  • Luciferases

Grants and funding

The study was financially supported by grants from the China Postdoctoral Science Foundation (Project Code: 2012M521588), http://jj.chinapostdoctor.org.cn/V1/Program1/Default.aspx. The funder had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.