MicroRNA-205 targets SMAD4 in non-small cell lung cancer and promotes lung cancer cell growth in vitro and in vivo
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Yuanyuan Zeng1,2,*, Jianjie Zhu1,2,*, Dan Shen1,*, Hualong Qin3, Zhe Lei4, Wei Li5, Zeyi Liu1,2, Jian-an Huang1,2
1Department of Respiratory Medicine, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
2Institute of Respiratory Diseases, Soochow University, Suzhou, P. R. China
3Department of Cardiothoracic Surgery, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
4Suzhou Key Laboratory for Molecular Cancer Genetics, Suzhou, P. R. China
5Department of Oncology, The First Affiliated Hospital of Soochow University, Suzhou, P. R. China
*These authors contributed equally to this work
Zeyi Liu, email: [email protected]
Jian-an Huang, email: [email protected]
Keywords: SMAD4, miR-205, NSCLC, proliferation, cell cycle
Received: March 20, 2016 Accepted: June 13, 2016 Published: June 30, 2016
Despite advances in diagnosis and treatment, the survival of non-small cell lung cancer (NSCLC) patients remains poor; therefore, improved understanding of the disease mechanism and novel treatment strategies are needed. Downregulation of SMAD4 and dysregulated expression of miR-205 have been reported. However, the relationship between them remains unclear. We investigated the effect of microRNA (miR)-205 on the expression of SMAD4 in NSCLC. Knockdown and overexpression of SMAD4 promoted or suppressed cellular viability and proliferation, and accelerated or inhibited the cell cycle in NSCLC cells, respectively. The 3′-untranslated region (3′-UTR) of SMAD4 was predicted as a target of miR-205. Luciferase assays validated that miR-205 binds directly to the SMAD4 3′-UTR. Protein and mRNA expression analyses confirmed that miR-205 overexpression in NSCLC cells inhibited the expression of SMAD4 mRNA and protein. In human NSCLC tissues, increased miR-205 expression was observed frequently and was inversely correlated with decreased SMAD4 expression. Ectopic expression of miR-205 in NSCLC cells suppressed cellular viability and proliferation, accelerated the cell cycle, and promoted tumor growth of lung carcinoma xenografts in nude mice. Our study showed that miR-205 decreased SMAD4 expression, thus promoting NSCLC cell growth. Our findings highlighted the therapeutic potential of targeting miR-205 in NSCLC treatment.
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