UHRF1, an epigenetic factor, is implicated in various cellular processes of tumorigenesis. However, the modulation UHRF1 expression in human bladder cancer at posttranscriptional levels remains unclear.
Here, we report that miR-124 suppresses expression of UHRF1 to affect the progression of human bladder cancer through competitive binding the same region of its 3'UTR. We showed that compared with corresponding normal tissues, UHRF1 was upregulated and miR-124 was downregulated in bladder cancer tissues, demonstrating an inverse correlation of miR-124 and UHRF1. Quantitative PCR and western blot assay demonstrated that over-expression of miR-124 resulted in the suppression of UHRF1. Furthermore, luciferase assay revealed that miR-124 could control the fate of target gene UHRF1 mRNA by binding 3'-UTR. The rescue experiment confirmed that miR-124 exerted its biological functions by targeting UHRF1. MiR-124 over-expression significantly attenuated cellular proliferation, migration, invasion and vasculogenic mimicry in vitro, and tumor growth in vivo. UHRF1 siRNA showed significant inhibitory effects on bladder cancer cells. Collectively, our study demonstrated that miR-124 can impair the proliferation, matastasis of human bladder cancer cells by down-regulation of UHRF1. This article is protected by copyright. All rights reserved.
The FEBS journal 2015 Aug 27 [Epub ahead of print]
Xinsheng Wang, Qiaoli Wu, Bin Xu, Pengfei Wang, Weijia Fan, Ying Cai, Xinquan Gu, Fanping Meng
Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, P R China , Tianjin Neurosurgery Institute, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory, Tianjin Huanhu Hospital, Tianjin, 300060, P R China , The Graduate School, Tianjin Medical University, Tianjin, 300070, P R China , The Graduate School, Tianjin Medical University, Tianjin, 300070, P R China , Tianjin Neurosurgery Institute, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory, Tianjin Huanhu Hospital, Tianjin, 300060, P R China , Tianjin Neurosurgery Institute, Tianjin Cerebral Vascular and Neural Degenerative Disease Key Laboratory, Tianjin Huanhu Hospital, Tianjin, 300060, P R China , Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, P R China , Department of Urology, China-Japan Union Hospital of Jilin University, Changchun, Jilin, 130033, P R China