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

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

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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Published
2017-05-03
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Section
Original Papers
Supporting Agencies
Program of Shanghai City Committee of Science and Technology (15DZ1941502, key disciplines group construction project of Pudong Health Bureau of Shanghai (PWZxq2014-11)
Keywords:
Benign prostatic hyperplasia, EMT, DNMT1, methylation
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How to Cite
Xu, H., Chen, Y., Chen, Q., Xu, H., Wang, Y., Yu, J., Zhou, J., Wang, Z., & Xu, B. (2017). DNMT1 regulates IL-6- and TGF-β1-induced epithelial mesenchymal transition in prostate epithelial cells. European Journal of Histochemistry, 61(2). https://doi.org/10.4081/ejh.2017.2775