MiR-200a-3p predicts prognosis and inhibits bladder cancer cell proliferation by targeting STAT4.

Abstract

STAT4 is a transcriptional regulator that has been reported to have oncogenic activities in various cancers. In our study, the posttranscriptional regulatory effect of miR-200a-3p on STAT4 and the prognostic significance of miR-200a-3p and STAT4 were evaluated in bladder cancer (BCa). Proliferation and apoptosis of BCa cell lines were monitored using CCK-8 and Annexin V-FITC assays, respectively. Gene and protein expression levels in BCa tissues and cells were detected using RT-qPCR and western blotting, respectively. Significant downregulation of miR-200a-3p and upregulation of STAT4 were observed in BCa tissues and cells compared with the corresponding non-tumor adjacent tissues. Both STAT4 and miR-200a-3p were validated as independent prognostic indicators in sixty-nine BCa patients for predicting overall survival and disease-free survival. In vitro experimental analyses revealed that knockdown of STAT4 repressed BCa cell growth and elevated cell apoptosis. Molecular interactive analysis revealed STAT4 as a direct target of miR-200a-3p, which could suppress STAT4 protein expression by posttranscriptional repression. Cotransfection of miR-200a-3p mimics and STAT4 overexpression plasmids into BCa cells demonstrated that the antineoplastic activities of miR-200a-3p in vitro were neutralized by overexpressed STAT4. The miR-200a-3p/STAT4 signaling cascade plays an important role in the progression of BCa, which provides a new promising target for targeted BCa therapies.