A novel regulatory circuit of miR‑152 and DNMT1 in human bladder cancer

Zhang,Haiqing; Qi,Defeng; Li,Jinhui; Peng,Tao; Yang,Linqing; Yuan,Jianhui; Zhang,Yuying; Hu,Yuan; Su,Jialin; Que,Biao; Li,Mengxi; Zhou,Guoren; Chen,Yuxin; Zhang,Wenjuan; Ji,Weidong

doi:10.3892/or.2018.6553

A novel regulatory circuit of miR‑152 and DNMT1 in human bladder cancer

Authors:
- Haiqing Zhang
- Defeng Qi
- Jinhui Li
- Tao Peng
- Linqing Yang
- Jianhui Yuan
- Yuying Zhang
- Yuan Hu
- Jialin Su
- Biao Que
- Mengxi Li
- Guoren Zhou
- Yuxin Chen
- Wenjuan Zhang
- Weidong Ji
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Affiliations: Center for Translational Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510230, P.R. China, Department of Urology, Minimally Invasive Surgery Center, Guangdong Key Laboratory of Urology, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, Guangdong 510230, P.R. China, Institute of Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, P.R. China, Institute of Toxicology, Shenzhen Center for Disease Control and Prevention, Shenzhen, Guangdong 518055, P.R. China, Center for Translational Medicine, The First Affiliated Hospital, Sun Yat‑sen University, Guangzhou, Guangdong 510080, P.R. China, Department of Medical Oncology, Jiangsu Cancer Hospital, Nanjing, Jiangsu 210009, P.R. China, Department of Laboratory Medicine, Nanjing Drum Tower Hospital, Nanjing, Jiangsu 210008, P.R. China, Department of Toxicology, School of Medicine, Jinan University, Guangzhou, Guangdong 510632, P.R. China
Published online on: July 10, 2018 https://doi.org/10.3892/or.2018.6553
Pages: 1803-1812

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Abstract

Downregulation of microRNA‑152 (miR‑152) has been observed in various types of human malignancies, including Bladder cancer (BC). However, the role of miR‑152 in the development and progression of BC is still unclear. In our previous study, we identified a functional crosstalk between miR‑152 and DNA methyltransferase 1 (DNMT1) involved in Nis‑induced malignant transformation. In the present study, we found that the expression of miR‑152 was specifically downregulated in BC cells and tissues via the DNA hypermethylation of the miR‑152 promoter. The overexpression of miR‑152 in BC cells resulted in a reduction of DNMT1, whereas the inhibition of the expression of miR‑152 induced an elevated level of DNMT1. Further studies revealed that miR‑152 directly downregulated the expression of DNMT1 by targeting the 3'‑UTR of its transcript in BC cells. In addition, ectopic expression of miR‑152 in BC cells significantly inhibited cell proliferation, whereas the inhibition of miR‑152 expression led to increased cell proliferation. These findings indicated a novel regulatory circuit of miR‑152/DNMT1 in BC, and more importantly, the combination of miR‑152 and DNMT1 may function as promising therapeutic modalities and early biomarkers for BC.

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