Downregulation of miR-638 promotes invasion and proliferation by regulating SOX2 and induces EMT in NSCLC

FEBS Lett. 2014 Jun 27;588(14):2238-45. doi: 10.1016/j.febslet.2014.05.002. Epub 2014 May 17.

Abstract

Aberrant expression of microRNAs has been shown to regulate the biological processes of lung cancer cells. However, the role of miR-638 in the development of NSCLC is still unclear. In this study, low miR-638 and high SOX2 were shown to be associated with tumor size and metastasis of NSCLC patients. Downregulated miR-638 could promote cell invasion and proliferation, while high miR-638 expression reversed the effect. Furthermore, miR-638 could regulate SOX2 by directly binding to its 3'-UTR. Silencing of SOX2 by siRNA partially abolished the enhancement of cell invasion and proliferation induced by downregulated miR-638. Aberrant miR-638 expression could modulate the expression levels of markers of epithelial-to-mesenchymal transition. Our results indicate that miR-638 may play a pivotal role in the development of NSCLC.

Keywords: Epithelial-to-mesenchymal transition; Invasion; Non-small-cell lung cancer; Proliferation; SRY (sex determining region Y)-box 2; miR-638.

MeSH terms

  • 3' Untranslated Regions
  • Apoptosis
  • Base Sequence
  • Binding Sites
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Carcinoma, Non-Small-Cell Lung / secondary
  • Cell Line, Tumor
  • Cell Proliferation*
  • Down-Regulation
  • Epithelial-Mesenchymal Transition*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / pathology
  • Male
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Middle Aged
  • Neoplasm Invasiveness
  • RNA Interference
  • SOXB1 Transcription Factors / genetics
  • SOXB1 Transcription Factors / metabolism*

Substances

  • 3' Untranslated Regions
  • MIRN638 microRNA, human
  • MicroRNAs
  • SOX2 protein, human
  • SOXB1 Transcription Factors