miR-200a-3p predicts prognosis and inhibits bladder cancer cell proliferation by targeting STAT4
Jie Li 1
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Department of Urology, the Fifth People’s Hospital of Dongguan, Dongguan, Guangdong Province, China
Submission date: 2019-05-29
Final revision date: 2019-09-27
Acceptance date: 2019-10-01
Online publication date: 2019-11-25
Arch Med Sci 2023;19(3)
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).

Material and methods:
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.