miR-145 and miR-497 suppress TGF-β-induced epithelial–mesenchymal transition of non-small cell lung cancer by targeting MTDH

Qi Yin, Yang Han, Dongyi Zhu, Zhanxia Li, Shan Shan, Wenjing Jin, Qingchun Lu, Tao Ren

MicroRNAs (miRNAs) have been reported to play crucial roles in multiple cancers including non-small cell lung cancer (NSCLC). Here, we investigated the role of miR-145 and miR-497 in TGF-β-induced epithelial-mesenchymal transition (EMT) process of NSCLC. We performed quantitative real time PCR (qRT-PCR) to detect the expression level of miR-145 and miR-497 in NSCLC cell lines. Then in the presence/absence of TGF-β, we transfected miRNA mimics or inhibitor into A549 and H1299 cells and investigated the role of miR-145 and miR-497 in cell migration and invasion using transwell and wound-healing assay. The regulation role of miR-145 and miR-497 on Metadherin (MTDH) was determined by luciferase assay. The expression level of MTDH and EMT markers E-cadherin and vimentin were detected on mRNA and protein level. In our study, our results showed that miR-145 and miR-497 were downregulated in NSCLC cell lines. Overexpression of miR-145 and miR-497 inhibited TGF-β-induced EMT and suppressed cancer cell migration and invasion, while the opposite results were observed in cells transfected with miR-145 or miR-497 inhibitor. Moreover, the luciferase assay confirmed that miR-145 and miR-497 attenuated MTDH expression by directly binding 3'-UTR of MTDH mRNA and exert the tumor-suppression role. Overall, we demonstrated that miR-145 and miR-497 functioned as EMT-suppressor in NSCLC by targeting MTDH, provided new evidence that miR-145 and miR-497 as potential therapeutic targets.