Up-Regulation of MiR-452 Inhibits Metastasis of Non-Small Cell Lung Cancer by Regulating BMI1

Cell Physiol Biochem. 2015;37(1):387-98. doi: 10.1159/000430362. Epub 2015 Aug 27.

Abstract

Background/aims: MicroRNAs (miRNAs) have been regarded as a new class of regulators in cellular processes in non-small cell lung cancer (NSCLC). However, the relationship between miR-452 and the development of NSCLC remains unclear.

Methods: qRT-PCR was used to detect the expression of miR-452 and its target gene in NSCLC samples (n=60). The transwell assay was used to test the cell invasion capability. The regulation mechanism was confirmed by luciferase reporter assay and western blot assay.

Results: In the current study, a relatively lower miR-452 and higher BMI1 expression levels were confirmed to be associated with advanced tumor stage and more extent of lymph nodes metastasis. In vitro, down-regulated miR-452 could enhance cell invasion capability. Furthermore, miR-452 modulated BMI1 expression by binding to its 3'-UTR. The enhancement of cell invasion capability induced by down-regulated miR-452 was eliminated by repression of BMI1.

Conclusions: Our results suggest that miR-452 plays a vital role in development of NSCLC, and this miR-452-BMI1 pathway might generate a novel insight into the treatment of NSCLC.

MeSH terms

  • 3' Untranslated Regions / genetics
  • Carcinoma, Non-Small-Cell Lung / genetics*
  • Carcinoma, Non-Small-Cell Lung / pathology
  • Cell Line, Tumor
  • Down-Regulation / genetics
  • Gene Expression Regulation, Neoplastic / genetics
  • Humans
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Lymphatic Metastasis / genetics*
  • Lymphatic Metastasis / pathology
  • MicroRNAs / genetics*
  • Neoplasm Invasiveness / genetics
  • Neoplasm Invasiveness / pathology
  • Polycomb Repressive Complex 1 / genetics*
  • Up-Regulation / genetics*

Substances

  • 3' Untranslated Regions
  • BMI1 protein, human
  • MIRN452 microRNA, human
  • MicroRNAs
  • Polycomb Repressive Complex 1