Mechanism of epithelial‑mesenchymal transition inhibited by miR‑203 in non‑small cell lung cancer

The aim of the present study was to investigate whether miR203 can inhibit transforming growth factorbeta (TGFbeta)induced epithelialmesenchymal transition (EMT), and the migration and invasion ability of nonsmall cell lung cancer (NSCLC) cells by targeting SMAD3. In the present study, the expression levels of miR203, SMAD3 mRNA and protein in NSCLC tissues were examined, as well as their corresponding paracancerous samples. The miR203 mimics and miR203 inhibitor were transfected into the H226 cell line. RTqPCR was used to assess the expression levels of Ecadherin, Snail, Ncadherin and vimentin mRNA, and western blotting was performed to detect the expression levels of pSMAD2, SMAD2, pSMAD3, SMAD3 and SMAD4. The cell migration and invasion abilities were detected by Transwell assays. The target site of SMAD3 was predicted by the combined action between miR203 and dual luciferase. The results revealed that the RNA levels of miR203, compared with paracancerous tissues, were decreased in NSCLC tissues, while SMAD3 mRNA and protein levels were upregulated, and miR203 inhibited SMAD3 expression. Induction of TGFbeta led to decreased Ecadherin mRNA levels, upregulation of Snail, Ncadherin and vimentin mRNA levels (P<0.05), and significant increase in cell migration and invasion, whereas transfection of miR203 mimics reversed the aforementioned results (P<0.05). Conversely, miR203 inhibitor could further aggravate the aforementioned results (P<0.05). Western blot results revealed that transfection of miR203 mimics significantly reduced the protein expression of SMAD3 and pSMAD3 (P<0.05). Furthermore, the results of the DualLuciferase assay revealed that miR203 inhibited SMAD3 expression by interacting with specific regions of its 3'UTR. Overall, a novel mechanism is revealed, in which, miR203 can inhibit SMAD3 by interacting with specific regions of the 3'UTR of SMAD3, thereby restraining TGFbetainduced EMT progression and migration and invasion of NSCLC cells.