MicroRNA-133b inhibits the growth of non-small-cell lung cancer by targeting the epidermal growth factor receptor

FEBS J. 2012 Oct;279(20):3800-12. doi: 10.1111/j.1742-4658.2012.08741.x. Epub 2012 Sep 11.

Abstract

Both the deregulation of microRNAs and epidermal growth factor receptor (EGFR) are emerging as important factors in non-small-cell lung cancer (NSCLC). Here, miR-133b was found to be associated with tumor stage, the extent of regional lymph node involvement, stage, visceral pleura or vessel invasion and EGFR mRNA expression in Chinese patients with NSCLC. Bioinformatic analysis and luciferase reporter assay revealed that miR-133b can interact specifically with the 3'-UTR of EGFR mRNA. Functionally, miR-133b transfection showed regulatory activity in translationally repressing EGFR mRNA. Moreover, miR-133b transfection may modulate apoptosis, invasion and sensitivity to EGFR-TKI through the EGFR signaling pathways, especially in EGFR-addicted NSCLC cells. Taken together, our findings show that miR-133b can inhibit cell growth of NSCLC through targeting EGFR and regulating its downstream signaling pathway. This finding has important implications for the development of targeted therapeutics for a number of EGFR-addicted cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3' Untranslated Regions / genetics
  • Apoptosis / genetics
  • Blotting, Western
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / metabolism
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Movement / genetics
  • Cell Proliferation*
  • Cell Survival / drug effects
  • Cell Survival / genetics
  • ErbB Receptors / genetics*
  • ErbB Receptors / metabolism
  • Female
  • Gefitinib
  • Gene Expression Regulation, Neoplastic
  • HEK293 Cells
  • Humans
  • In Situ Hybridization
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / metabolism
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Staging
  • Protein Kinase Inhibitors / pharmacology
  • Quinazolines / pharmacology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Signal Transduction / drug effects
  • Signal Transduction / genetics

Substances

  • 3' Untranslated Regions
  • MIRN133 microRNA, human
  • MicroRNAs
  • Protein Kinase Inhibitors
  • Quinazolines
  • RNA, Messenger
  • ErbB Receptors
  • Gefitinib