Pathologically decreased expression of MIR-193a contributes to metastasis by targeting WT1-E-cadherin axis in non-small cell lung cancers

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 of wt1 resembled the anti-cancer activity by mir-193a and overexpression of wt1 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. © 2016 the author(s).