MicroRNA-31 Inhibits Lung Adenocarcinoma Stem-Like Cells via Down-Regulation of MET-PI3K-Akt Signaling Pathway

Author(s): Chunying Hou, Bo Sun, Yao Jiang, Ji Zheng, Nan Yang, Chao Ji, Zhen Liang, Jiaojiao Shi, Rui Zhang, Yanyong Liu, Caiying Ye, Pingping Zuo.

Journal Name: Anti-Cancer Agents in Medicinal Chemistry

Volume 16 , Issue 4 , 2016

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Abstract:

Accumulated evidences suggested that microRNAs (miRs) play an important role in non-small cell lung cancer (NSCLC). However, how miRs perform their functions in lung adenocarcinoma cancer stem cells (CSCs) remains unknown. Notably, most studies pay more attention to the effects of miRNAs on the metastasis traits whereas the growth activities of CSCs are rather undervalued. In our report, using A549CD133+cells, we examined the inhibitory effects and the underlying mechanisms of microRNA-31 (miR-31) on the growth of lung adenocarcinoma CSC-like cells. Initially, we determined the level of miR-31 in A549 and A549CD133+ cells. Over-expression of miR-31 was found in A549CD133+ cells by microarray and real-time quantitative PCR (RTqPCR) assays. Experiments in multiple NSCLC cell lines in vitro and A549CD133+ cells xenograft models in vivo confirmed that down regulation of miR-31 resulted in increase of A549CD133+ cells growth, whereas overexpression of miR-31 led to the inhibition of adenocarcinoma cell proliferation. Also, MET proto-oncogene has been determined to be a direct target of miR-31 by dual luciferase report, RT-qPCR and western blot analysis. Down regulation of MET inhibited viability of A549CD133+ cells. The levels of PI3Kinase, Akt and p-Akt as well as downstream proteins were consequently decreased. These results suggest that miR-31 might inhibit the growth of lung adenocarcinoma cancer stem-like cells via down regulation of the MET-PI3K-Akt signaling pathway.

Keywords: Cancer stem cells (CSCs), MET, microRNA-31 (miR-31), non-small cell lung cancer (NSCLC), PI3K-Akt signaling pathway.

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Article Details

VOLUME: 16
ISSUE: 4
Year: 2016
Page: [501 - 518]
Pages: 18
DOI: 10.2174/1871520615666150824152353
Price: $58

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