Hypermethylation of the GRHL2 promoter region is associated with ovarian endometriosis

Yali Hao, Yan Li, Jianlei Wu, Na Hao, Yuzhen Qin, Haibo Zhang, Wei Zhao, Shan Kang
Reproduction (Cambridge, England) · 2022 · vol. 163(6) , pp. 379–386 · doi:10.1530/rep-21-0383 · PMID:35356893 · W4220681443
article OA: closed CC0 ⤵ 2 in-corpus citations
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This study found that hypermethylation of the GRHL2 promoter region in ectopic endometrium of ovarian endometriosis patients correlates with decreased GRHL2 expression and increased invasion and migration of endometrial cells.

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Abstract

Abnormal gene expression caused by epigenetic changes, including DNA methylation, is associated with the development and progression of endometriosis. Grainyhead-like 2 gene (GRHL2), a suppressor of epithelial-mesenchymal transition, has been suggested to be associated with the occurrence, progression and poor survival of a variety of cancers. Although endometriosis is a benign disease, it has the biological behaviour of migration and invasion as malignant tumor. This study aims to determine whether the abnormal expression of the GRHL2 caused by aberrant methylation of its promoter is associated with the pathogenesis of ovarian endometriosis. Our results demonstrated that GRHL2 promoter region was significantly hypermethylated in the ectopic endometrium of patients with ovarian endometriosis compared with the normal endometrium of control patients. In contrast, the levels of GRHL2 mRNA and protein were significantly lower in the ectopic endometrium than in the control endometrium. Correlation analysis showed the methylation levels of GRHL2 were significantly negatively correlated with the mRNA expression of GRHL2. Moreover, the in vitro results suggested that the knockdown of GRHL2 could significantly increase the invasion and migration ability of EECs and may promote ZEB1 and vimentin expression while decreasing the expression of E-cadherin in EECs. Taken together, these results suggest that the low expression of GRHL2 caused by hypermethylation of the GRHL2 promoter is associated with ovarian endometriosis. The knockdown of GRHL2 may be involved in the occurrence of endometriosis by increasing EEC migration and invasion. This study provides more evidence for the hypothesis that endometriosis may be an epigenetic regulatory disorder.

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Condition tags

endometriosis

MeSH descriptors

Endometriosis Endometriosis Endometriosis Endometriosis Endometriosis Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms Ovarian Neoplasms DNA-Binding Proteins DNA-Binding Proteins DNA-Binding Proteins DNA-Binding Proteins DNA-Binding Proteins DNA-Binding Proteins DNA Methylation DNA Methylation DNA Methylation DNA Methylation

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