J Cancer 2019; 10(12):2735-2744. doi:10.7150/jca.31800

Research Paper

MiR-940 inhibits TGF-β-induced epithelial-mesenchymal transition and cell invasion by targeting Snail in non-small cell lung cancer

Kanqiu Jiang1,*, Ting Zhao1,*, Mingjing Shen1, Fuquan Zhang1, Shanzhou Duan1, Zhe Lei2,3,✉, Yongbing Chen1,✉

1. Department of Thoracic and Cardiovascular Surgery, The Second Affiliated Hospital of Soochow University, Medical College of Soochow University, Suzhou 215004, China
2. Soochow University Laboratory of Cancer Molecular Genetics, Medical College of Soochow University, Suzhou 215123, China
3. Department of Genetics, School of Biology and Basic Medical Science, Medical College of Soochow University, Suzhou, Jiangsu, 215123, China
* These authors contributed equally to this work.

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Citation:
Jiang K, Zhao T, Shen M, Zhang F, Duan S, Lei Z, Chen Y. MiR-940 inhibits TGF-β-induced epithelial-mesenchymal transition and cell invasion by targeting Snail in non-small cell lung cancer. J Cancer 2019; 10(12):2735-2744. doi:10.7150/jca.31800. Available from http://www.jcancer.org/v10p2735.htm

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Abstract

Increased evidence reveals that miR-940 inhibits the migration and invasion of cancer cells. Considering transforming growth factor β (TGF-β) signaling is crucial to cellular epithelial-mesenchymal transition (EMT) process and metastasis of cancer, it is in urgent to explore whether and how miR-940 plays an essential role in regulating TGF-β-induced EMT in lung cancer progression. In the present study, we observed a reciprocal expression with down-regulated miR-940 and up-regulated Snail mRNA in non-small-cell lung cancer (NSCLC) tissues. we further found that the expression of miR-940 was decreased in NSCLC tissues with lymph node metastasis, advanced TNM stages and poor cell differentiation, in which, on the contrary, the expression of Snail was increased. Overexpression of miR-940 significantly inhibited Snail mRNA and protein expression in A549 and H226 cells. Mechanistically, Snail mRNA was identified as target of miR-940. In addition, miR-940 repressed TGF-β-induced EMT and further hampered the cell migration and invasion. Finally, siRNA-mediated knockdown of Snail copied the phenotype of miR-940 overexpression in A549 and H226 cells. Taken together, our study reveals that miR-940 can suppress TGF-β-induced EMT and cell invasion by targeting Snail 3'-UTR mRNA in NSCLC.

Keywords: NSCLC, EMT, transforming growth factor beta, microRNA, SNAI1