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DNMT1 regulates IL-6- and TGF-β1-induced epithelial mesenchymal transition in prostate epithelial cells

Hui Xu, Yanbo Chen, Qi Chen, Huan Xu, Yanxia Wang, Jiao Yu, Juan Zhou, Zhong Wang, Bing Xu
  • Hui Xu
    Department of Emergency, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, China
  • Yanbo Chen
    Department of Urology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine,
  • Qi Chen
    Department of Urology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine,
  • Huan Xu
    Department of Urology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai, China,
  • Yanxia Wang
    Department of Emergency, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine,
  • Jiao Yu
    Department of Emergency, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine,
  • Juan Zhou
    Department of Urology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine,
  • Zhong Wang
    Department of Urology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine, | 0127239252@sjtu.edu.cn
  • Bing Xu
    Department of Emergency, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiaotong University School of Medicine,

Abstract

Multiple factors have been considered to play a role in the development of benign prostatic hyperplasia (BPH), including chronic inflammation, hormones, and epithelial-mesenchymal transition (EMT). Inflammation is regarded as one of the potential inducers of EMT. However, the mechanisms, modulating pro-inflammatory factors (IL-6 and TGF-β1) induce EMT features, have not yet been studied in BPH. In this study, we investigated whether DNA methyltransferases1 (DNMT1) could regulate IL-6 and TGF-β1 induce EMT. The expression of EMT features was analyzed in normal prostate epithelial cells (PrECs) and BPH1 cells. Real-time RT-PCR and western blotting were used to examine the expression of EMT features in IL-6- and TGF-β1-treated PrECs. Next, bisulfite sequencing PCR (BSP) methods were used to examine the DNA methylation level of the Cdh1 promoter region. The results showed that EMT features were increased in BPH1 cells, compared to PrECs. IL-6 and TGF-β1 treatment induced EMT features, including decreased E-cadherin expression. The results of BSP revealed significant DNA hypermethylation at the promoter region of Cdh1 after IL-6 and TGF-β1 exposure, which was rescued when pretreated with 5-Aza or TGF-β1 antibody. Moreover, the protein expression and methyltransferase activity of DNMT1 were also increased after IL-6 and TGF-β1 induction. Collectively, our study showed that IL-6 and TGF-β1 could activate DNMT1 and directly regulate the expression of E-cadherin in PrECs, providing a potential therapeutic candidate for BPH. 

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Submitted: 2017-01-28 05:31:11
Published: 2017-05-03 11:55:07
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Copyright (c) 2017 Hui Xu, Yanbo Chen, Qi Chen, Huan Xu, Yanxia Wang, Jiao Yu, Juan Zhou, Zhong Wang, Bing Xu

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