MiR-145 and miR-203 represses TGF-β-induced epithelial-mesenchymal transition and invasion by inhibiting SMAD3 in non-small cell lung cancer cells

• Both miR-145 and miR-203 reduces SMAD3 expression by targeting SMAD3 3′-UTR.
• MiR-145 and miR-203 inhibits TGF-β-induced EMT and invasion in NSCLC cells.
• Knockdown of SMAD3 suppresses TGF-β-induced EMT and invasion of NSCLC cells.
• MiR-145/miR-203 is under-expressed while SMAD3 mRNA is up-expressed in NSCLC tissues.

ObjectivesMicroRNAs (miRNAs) have been proved to play important role in development of various cancers, including non-small cell lung cancer (NSCLC). Our previous studies have shown that miR-203 and miR-145 are associated with cellular invasion in NSCLC and nasopharyngeal cancer, respectively. However, the mechanistic role of miR-203 and miR-145 in TGF-β-induced epithelial-mesenchymal transition (EMT) has not yet been elucidated in human cancers, including NSCLC.Materials and methodsReal-time quantitative reverse transcriptase PCR (qRT-PCR), western blot analysis, luciferase reporter gene assays, small RNA interference and transwell migration and invasion assays were carried on human NSCLC cell lines A549 and 95C. Thirty-six paired NSCLC tissues and adjacent noncancerous lung tissues were collected.ResultsBoth miR-145 and miR-203 can directly target the 3′-untranslated region (3′-UTR) of SMAD3, and overexpression of the two miRNAs in NSCLC cells inhibited the expression of SMAD3 mRNA and protein, whereas inhibition of endogenous miR-145 or miR-203 caused an increased expression of SMAD3. Moreover, miR-145 and/or miR-203 repressed TGF-β-induced EMT and attenuated cell migration and invasion in A549 and 95C cells. siRNA-mediated knockdown of SMAD3 copied the phenotype of miR-145 and miR-203 overexpression in A549 and 95C cells.ConclusionMiR-145 and miR-203 inhibited TGF-β-induced EMT and invasion through repression of SMAD3 in NSCLC cells. Our findings provided insights into the miRNA-based mechanism for controlling TGF-β-induced EMT of NSCLC cells and a strategy for targeted therapy of NSCLC.