TET1 may contribute to hypoxia-induced epithelial to mesenchymal transition of endometrial epithelial cells in endometriosis.

Abstract:

Background:Endometriosis (EMs) is a non-malignant gynecological disease, whose pathogenesis remains to be clarified. Recent studies have found that hypoxia induces epithelial-mesenchymal transition (EMT) as well as epigenetic modification in EMs. However, the relationship between EMT and demethylation modification under hypoxia status in EMs remains unknown. Methods:The expression of N-cadherin, E-cadherin and TET1 in normal endometria, eutopic endometria and ovarian endometriomas was assessed by immunohistochemistry and immunofluorescence double staining. 5-hmC was detected by fluorescence-based ELISA kit using a specific 5-hmC antibody. Overexpression and inhibition of TET1 or hypoxia-inducible factor 2α (HIF-2α) were performed by plasmid and siRNA transfection. The expression of HIF-2α, TET1 and EMT markers in Ishikawa (ISK) cells (widely used as endometrial epithelial cells) was evaluated by western blotting. The interaction of HIF-2α and TET1 was analyzed by chromatin immunoprecipitation. Results:Demethylation enzyme TET1 (ten-eleven translocation1) was elevated in glandular epithelium of ovarian endometrioma, along with the activation of EMT (increased expression of N-cadherin, and decreased expression of E-cadherin) and global increase of epigenetic modification marker 5-hmC(5-hydroxymethylcytosine). Besides, endometriosis lesions had more TET1 and N-cadherin co-localized cells. Further study showed that ISK cells exhibited enhanced EMT, and increased expression of TET1 and HIF-2α under hypoxic condition. Hypoxia-induced EMT was partly regulated by TET1 and HIF-2α. HIF-2α inhibition mitigated TET1 expression changes provoked by hypoxia. Conclusions:Hypoxia induces the expression of TET1 regulated by HIF-2α, thus may promote EMT in endometriosis.

journal_name

PeerJ

journal_title

PeerJ

authors

Wu J,Li X,Huang H,Xia X,Zhang M,Fang X

doi

10.7717/peerj.9950

subject

Has Abstract

pub_date

2020-09-15 00:00:00

pages

e9950

issn

2167-8359

pii

9950

journal_volume

8

pub_type

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