A novel pathway in NSCLC cells: miR-191, targeting NFIA, is induced by chronic hypoxia, and promotes cell proliferation and migration

作者：Zhao, Jia; Qiao, Cheng-Rui; Ding, Zheng; Sheng, Yin-Liang; Li, Xiang-Nan; Yang, Yang; Zhu, Deng-Yan; Zhang, Chun-Yang; Liu, Dong-Lei; Wu, Kai; Zhao, Song^*

来源：Molecular Medicine Reports, 2017, 15(3): 1319-1325.

DOI：10.3892/mmr.2017.6100

• microRNA-191
• non-small cell lung cancer
• chronic hypoxia
• proliferation and migration
• nuclear factor 1 alpha

MicroRNAs (miRs) have emerged as being important in cancer biology. miR-191 is a conserved miRNA, which has been investigated in detail and is reported to be induced by hypoxia-inducible factor (HIF)-1 alpha and has an contributory action in the progression of breast, hepatic and pancreatic cancer. However, the effects of miR-191 in the progression of lung cancer are a subject of debate. In the present study, it was found that the expression of miR-191 was significantly upregulated in non-small cell lung cancer (NSCLC) cells in patients in vivo. However, the levels of miR-191 remained unchanged in SK-MES-1, A549 and NCI-H460 NSCLC cell lines, compared with the level in the normal HBE lung cell line, however, the levels were markedly upregulated in these NSCLC cell lines under conditions of chronic hypoxia. Subsequently, an miR-191 mimic was transfected into the NSCLC cell lines to examine its effect on the progression of the NSCLC cells in vitro. The data obtained using MTT and Cell counting kit-8 assays revealed that miR-191 had no effect on the proliferation of the cells under normal condition, however, their proliferation was promoted under mild hypoxic conditions. In addition, the results of a Transwell migration assay showed that miR-191 had a promoting effect on NSCLC cell migration under the conditions of chronic hypoxia. Furthermore, the TargetScan bioinformatics server and 3'-untranslated region luciferase reporter assay indicated that the transcription factor, nuclear factor 1 alpha (NFIA) was a target of miR-191. Subsequent western blot analysis showed that, in chronic-hypoxia, the protein levels of NFIA and the tumor suppressor, CCAAT-enhancer-binding protein a, were sharply reduced in A549 cells. In conclusion, miR-191 was induced by chronic hypoxia and promoted the proliferation and migration of NSCLC cells under chronic hypoxic conditions. This promotion may be associated with its targeting of NFIA. The present findings may provide a potential molecular target for the therapeutic treatment of NSCLC.

• 出版日期2017-3
• 单位郑州大学