Hsa-miR-429 Promotes Bladder Cancer Cell Proliferation Via Inhibiting CDKN2B

[Purpose] Bladder cancer is the ninth most common malignancy all over the world and it is estimated that there are 386,000 new cases are diagnosed worldwide annually.Emerging evidences have indicated that microRNA are pivotal regulators of tumor development and progression.Hsa-miR-429 is a novel microRNA that acts as a potential biomarker and involves in development of multiple cancers.However,the clinical significance and molecular mechanism of Hsa-miR-429 in bladder cancer is still unknown.In this study,we aimed to figure out the role of Hsa-miR-429 in bladder cancer.[Methods] The expression levels of hsa-miR-429 and cyclin-dependentkinase inhibitor 2B(CDKN2B)were determined using Real-Time qPCR in a total of 50 patients with bladder cancer.Bladder cancer T24 and 5637 cells were transfected CDKN2 B siRNA or hsa-miR-429 mimic.CDKN2 B expression levels after transfection were detected by Real-Time qPCR and Western blot assay respectively.Binding sites between hsa-miR-429 and 3’-untranslated region of CDKN2 B were confirmed by Dual luciferase reporter assay.Cell proliferation was evaluated using MTT and EdU assays.Cell apoptosis was determined using ELISA assay.[Results] Higher hsa-miR-429 expression levels were associated with higher tumor grade and stage.All patients with low hsa-miR-429 expression survived5 years,while with high hsa-miR-429 expression,only 58% survived.Hsa-miR-429 and CDKN2 B were inversely expressed in bladder cancer.Hsa-miR-429 mimic decreased the expression of CDKN2 B at both mRNA and protein levels.The binding site was confirmed between hsa-miR-429 and3’-untranslated region of CDKN2 B.Up-regulation of hsa-miR-429 or down-regulation of CDKN2 B promoted cell growth and decreased apoptosis.[Conclusions] Our data suggest a mechanism for hsa-miR-429 to play oncogenic roles via inhibiting CDKN2 B,which may help to understand the mechanism of bladder cancer development.