Hsa-miR-429 promotes bladder cancer cell proliferation via inhibiting CDKN2B

Jiangeng Yang; Yuchen Liu; Anbang He; Yuhan Liu; Jianting Wu; Xinhui Liao; Zhaojie Lv; Feng Wang; Hongbing Mei

doi:10.18632/oncotarget.19878

Hsa-miR-429 promotes bladder cancer cell proliferation via inhibiting CDKN2B

Oncotarget. 2017 Aug 3;8(40):68721-68729. doi: 10.18632/oncotarget.19878. eCollection 2017 Sep 15.

Authors

Jiangeng Yang^{1

2}, Yuchen Liu^{1

2}, Anbang He^{1

2

3}, Yuhan Liu¹, Jianting Wu¹, Xinhui Liao¹, Zhaojie Lv¹, Feng Wang¹, Hongbing Mei^{1

2}

Affiliations

¹ Department of Urology, Shenzhen Second People's Hospital, Clinical Institute of Guangzhou Medical University, Shenzhen 518039, Guangdong Province, China.
² Key Laboratory of Medical Reprogramming Technology, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University Shenzhen, Guangdong Province, China.
³ Anhui Medical University, Anhui, China.

Abstract

Background and objectives: Hsa-miR-429 is increased in bladder cancer. Its roles in bladder cancer are poorly understood.

Methods: The expression levels of hsa-miR-429 and cyclin-dependent kinase 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 CDKN2B siRNA or hsa-miR-429 mimic. CDKN2B 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 CDKN2B 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 survived 5 years, while with high hsa-miR-429 expression, only 58% survived. Hsa-miR-429 and CDKN2B were inversely expressed in bladder cancer. Hsa-miR-429 mimic decreased the expression of CDKN2B at both mRNA and protein levels. The binding site was confirmed between hsa-miR-429 and 3'-untranslated region of CDKN2B. Up-regulation of hsa-miR-429 or down-regulation of CDKN2B promoted cell growth and decreased apoptosis.

Conclusions: Our data suggest a mechanism for hsa-miR-429 to play oncogenic roles via inhibiting CDKN2B.

Keywords: cyclin-dependent kinase inhibitor 2B; microRNA; urothelial carcinoma.