MiR-497 Suppresses YAP1 and Inhibits Tumor Growth in Non-Small Cell Lung Cancer

Cell Physiol Biochem. 2015;37(1):342-52. doi: 10.1159/000430358. Epub 2015 Aug 24.

Abstract

Background/aims: To investigate the expression, clinical significance and the cellular effects of miR-497 in non-small cell lung cancer (NSCLC).

Methods: NSCLC cells were transiently transfected with miR-497 mimics or siRNA to up-regulate or down-regulate expression. Quantitative real-time PCR (qRT-PCR) was used to detect the mRNA level of miR-497. Luciferase assays, colony formation assays and BrdU incorporation assays were performed to identify the targets and role of miR-497 in NSCLC cells. Finally, the abundance of miR-497 was analyzed in a total of 51 NSCLC specimens.

Results: The transcript levels of miR-497 were significantly decreased in NSCLC tissue (25/30; 83.3%). Low miR-497 levels in tumor tissue correlated with advanced pT stage. Additionally, miR-497 transcript levels correlated with overall survival of NSCLC patients (n = 51, p = 0.022). Overexpression of miR-497 inhibited the proliferation of NSCLC cell and down-regulation of miR-497 resulted in elevated NSCLC growth. Exogenous over-expression of YAP1 partially eliminated miR-497-induced cell growth.

Conclusion: miR-497 plays an important role in inhibiting the proliferation of NSCLC by targeting YAP1. Our results suggest that miR-497 is a potential therapeutic target in treating patients with NSCLC.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adaptor Proteins, Signal Transducing / genetics*
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Proliferation / genetics*
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • MicroRNAs / genetics*
  • Phosphoproteins / genetics*
  • RNA, Messenger / genetics
  • Transcription Factors
  • Up-Regulation / genetics
  • YAP-Signaling Proteins

Substances

  • Adaptor Proteins, Signal Transducing
  • MIRN497 microRNA, human
  • MicroRNAs
  • Phosphoproteins
  • RNA, Messenger
  • Transcription Factors
  • YAP-Signaling Proteins
  • YAP1 protein, human