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DNMT1 regulates IL-6- and TGF-β1-induced epithelial mesenchymal transition in prostate epithelial cells
- Source :
- European Journal of Histochemistry, Vol 61, Iss 2 (2017), European Journal of Histochemistry : EJH
- Publication Year :
- 2017
- Publisher :
- PAGEPress Publications, 2017.
-
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.
- Subjects :
- 0301 basic medicine
DNA (Cytosine-5-)-Methyltransferase 1
Male
Histology
Epithelial-Mesenchymal Transition
Bisulfite sequencing
Biophysics
Enzyme-Linked Immunosorbent Assay
Real-Time Polymerase Chain Reaction
CDH1
Cell Line
Transforming Growth Factor beta1
03 medical and health sciences
Humans
Epithelial–mesenchymal transition
lcsh:QH301-705.5
Original Paper
Benign prostatic hyperplasia
biology
Interleukin-6
DNMT1
EMT
Prostate
Epithelial Cells
Cell Biology
Cadherins
Blot
030104 developmental biology
Real-time polymerase chain reaction
lcsh:Biology (General)
Cell culture
DNA methylation
embryonic structures
biology.protein
Cancer research
methylation
Subjects
Details
- Language :
- English
- ISSN :
- 20388306
- Volume :
- 61
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- European Journal of Histochemistry
- Accession number :
- edsair.doi.dedup.....d729137fb9a3c9f39f8911b8dd7cce38