Pathologically decreased expression of miR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers. Issue 1 (December 2016)

• Record Type: Journal Article
• Authors: Chen, Junjie; Gao, Shenmeng; Wang, Chunjing; Wang, Zhonggai; Zhang, Huxiang; Huang, Kate; Zhou, Bin; Li, Haiying; Yu, Zhijie; Wu, Jianbo; Chen, Chengshui
• Is Part Of: Journal of experimental & clinical cancer research. Volume 35:Issue 1(2016)
• Page Start: 1
• Page End: 15
• Publication Date: 2016-12
• Subjects: MiR-193a -- Wilm's tumor-1 -- E-cadherin -- Epithelial-to-mesenchymal transition; Cancer -- Periodicals; 616.994005
• DOI: 10.1186/s13046-016-0450-8
• Languages: English
• ISSNs: 1756-9966

Abstract

Abstract Background The metastatic cascade is a complex and multistep process with many potential barriers. Recently, miR-193a has been reported to be a suppressive miRNA in multiple types of cancers, but its underlying anti-oncogenic activity in non-small cell lung cancers (NSCLC) is not fully elucidated. Methods The expressions of miR-193a (miR-193a-5p) in human lung cancer tissues and cell lines were detected by real-time PCR. Dual-luciferase reporter assay was used to identify the direct target of miR-193a. Cell proliferation, apoptosis, and metastasis were assessed by CCK-8, flow cytometry, and Transwell assay, respectively. Results The expression of miR-193a in lung cancer tissues was decreased comparing to adjacent non-tumor tissues due to DNA hypermethylation in lung cancer tissues. Ectopic expression of miR-193a inhibited cell proliferation, colony formation, migration, and invasion in A549 and H1299 cells. Moreover, overexpression of miR-193a partially reversed tumor growth factor-β1 (TGF-β1)-induced epithelial-to-mesenchymal transition (EMT) in NSCLC cells. Mechanistically, miR-193a reduced the expression of WT1, which negatively regulated the protein level of E-cadherin, suggesting that miR-193a might prevent EMT via modulating WT1-E-cadherin axis. Importantly, knockdown ofWT1 resembled the anti-cancer activity by miR-193a and overexpression ofWT1 partially reversed miR-193a-induced anti-cancer activity, indicating that WT1 plays an important role in miR-193a-induced anti-cancer activity. Finally, overexpression of miR-193a decreased the growth of tumor xenografts in mice. Conclusion Collectively, our results have revealed an important role of miR-193a-WT1-E-cadherin axis in metastasis, demonstrated an important molecular cue for EMT, and suggested a therapeutic strategy of restoring miR-193a expression in NSCLC.