Hypoxia-induced microRNA-301b regulates apoptosis by targeting Bim in lung cancer

Cell Prolif. 2016 Aug;49(4):476-83. doi: 10.1111/cpr.12264. Epub 2016 Jun 28.

Abstract

Objectives: Worldwide, lung cancer accounts for the majority of cancer-related deaths. Aberrant expression of miRNAs has increasingly been reported to be associated with tumour progression. This study aimed to explore the role of miR-301b in regulating apoptosis in lung cancer.

Materials and methods: Expression of miR-301b was assessed by real-time PCR in cell lines, human patient tissues and cells treated under hypoxia and DMOG. Scramble siRNA, miR-301b inhibitor and miR-301b mimics were transfected into lung cancer cells to determine their effects on apoptosis. Additionally, a mouse xenograft model was used to explore functions of miR-301b on apoptosis, in vivo. Finally, relationships between Bim and miR-301b levels were explored by luciferase reporter assay and Western blotting.

Results: We found that miR-301b was highly expressed in lung cancer tissues and cell lines. Expression of miR-301b was induced by hypoxia, and miR-301b suppressed expression of Bim by targeting its 3'UTR. Functionally, ectopic expression of miR-301b enhanced cell population growth, reduced apoptosis and reduced sensitivity of cells to chemotherapy. In the xenograft model, overexpression of miR-301b promoted tumour growth. Additionally, miR-301b and Bim expression were inversely correlated in clinical lung cancer samples.

Conclusions: This study provides new insights into the function of miRNA-301b in lung cancer and suggests that miRNA-301b could be a potential molecular target for chemotherapy.

MeSH terms

  • Animals
  • Apoptosis*
  • Bcl-2-Like Protein 11 / genetics*
  • Cell Line, Tumor
  • Cell Proliferation
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Hypoxia / complications
  • Hypoxia / genetics*
  • Hypoxia / pathology
  • Lung / metabolism
  • Lung / pathology
  • Lung Neoplasms / complications
  • Lung Neoplasms / genetics*
  • Lung Neoplasms / pathology
  • Mice
  • Mice, Nude
  • MicroRNAs / genetics*
  • Up-Regulation

Substances

  • Bcl-2-Like Protein 11
  • MIRN301A microRNA, human
  • MicroRNAs

Associated data

  • GENBANK/GSE25631
  • GENBANK/NM_001204106