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

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.

• Authors: Duoguang Wu, Baishen Chen, Fei Cui, Xiaotian He, Wenjian Wang, Minghui Wang
• Journal: Cell proliferation (Cell Prolif) Vol. 49 Issue 4 Pg. 476-83 (Aug 2016) ISSN: 1365-2184 [Electronic] England
• PMID: 27352910 (Publication Type: Journal Article)
• Copyright: © 2016 John Wiley & Sons Ltd.

Chemical References

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

Topics

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