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MicroRNA-138 acts as a tumor suppressor in non small cell lung cancer via targeting YAP1

Ling Xiao, Hui Zhou, Xiang-Ping Li, Juan Chen, Chao Fang, Chen-Xue Mao, Jia-Jia Cui, Wei Zhang, Hong-Hao Zhou, Ji-Ye Yin and Zhao-Qian Liu _

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Oncotarget. 2016; 7:40038-40046. https://doi.org/10.18632/oncotarget.9480

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Ling Xiao1,2,3, Hui Zhou4, Xiang-Ping Li1,2, Juan Chen1,2, Chao Fang1,2, Chen-Xue Mao1,2, Jia-Jia Cui1,2, Wei Zhang1,2, Hong-Hao Zhou1,2, Ji-Ye Yin1,2, Zhao-Qian Liu1,2

1Department of Clinical Pharmacology, Xiangya Hospital, Central South University, Hunan 410078, P.R. China

2Institute of Clinical Pharmacology, Central South University, Hunan Key Laboratory of Pharmacogenetics, Changsha, Hunan 410078, P.R. China

3Department of Histology and Embryology, School of Basic Medical Sciences, Central South University, Changsha, Hunan 410013, P.R. China

4The Affiliated Cancer Hospital, XiangYa School of Medicine, Central South University, Changsha, Hunan 410014, P.R. China

Correspondence to:

Zhao-Qian Liu, email: [email protected]

Ji-Ye Yin, email: [email protected]

Keywords: non small cell lung cancer, microRNA-138, Yes-associated protein 1, growth, metastasis

Received: December 08, 2015    Accepted: April 23, 2016    Published: May 19, 2016


MicroRNA (miR)-138 was found to have suppressive effects on the growth and metastasis of different human cancers. In this study, we aimed to investigate the regulatory mechanism of miR-138 in non-small cell lung cancer (NSCLC). We applied the Quantitative real-time PCR (qRT-PCR) to detect the miR-138 levels in NSCLC tissues (n=21) and cell lines, Bioinformatical predication, luciferase reporter assay and western blot to identify the target gene of miR-138. We also applied Cell transfection, MTT, transwell, and wound healing assays to reveal the role of miR-138 in NSCLC cell proliferation and malignant transformation. We observed that miR-138 expression level was significantly decreased in NSCLC tissues compared to their matched adjacent normal tissues. It was also downregulated in tissues with poor differentiation, advanced stage or lymph nodes metastasis, as well as in several NSCLC cell lines compared to normal lung epithelial cell. We further identified YAP1 as a direct target gene of miR-138, and observed that the protein level of YAP1 was negatively mediated by miR-138 in NSCLC A549 cells. Moreover, overexpression of miR-138 significantly inhibited A549 cell growth, invasion and migration, while knockdown of miR-138 enhanced such capacities. Further investigation showed that the cell proliferation capacity was higher in the miR-138+YAP1 group, when compared with that in the miR-138 group, suggesting that overexpression of YAP1 rescued the suppressive effects of miR-138 upregulation on NSCLC cell proliferation. However, we found no difference of cell invasion and migration capacities between miR-138+YAP1 group and miR-138 group. Finally, YAP1 was markedly upregulated in NSCLC tissues compared to their marched adjacent normal tissues. Its mRNA levels were reversely correlated with the miR-138 levels in NSCLC tissues. In summary, our study suggests that miR-138 may play a suppressive role in the growth and metastasis of NSCLC cells partly at least by targeting YAP1.

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