Hypomethylation of the ENPP3 promoter region contributes to the occurrence and development of ovarian endometriosis via the AKT/mTOR/4EBP1 signaling pathway

Authors

  • Yuzhen Qin Department of Obstetrics, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
  • Yishuai Li Department of Thoracic Surgery, Hebei Chest Hospital, Shijiazhuang, China
  • Yali Hao Department of Reproductive Medicine, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
  • Yan Li Department of Molecular Biology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China
  • Shan Kang Department of Gynecology, The Fourth Hospital of Hebei Medical University, Shijiazhuang, China

DOI:

https://doi.org/10.17305/bb.2023.9989

Keywords:

ENPP3, endometriosis, DNA methylation, epigenetic, transcriptome sequencing analysis

Abstract

Growing evidence indicates that aberrant methylation is pivotal in the development and progression of endometriosis (EMs). This study explores the relationship between abnormal methylation of the ENPP3 promoter and the pathogenesis of ovarian EMs, focusing on its regulatory effect on ENPP3 expression. We analyzed the methylation levels of ENPP3 in ectopic endometrial tissues from ovarian EMs patients and in normal endometrial tissues from women without EMs. The expression and distribution of ENPP3 were evaluated using RT-qPCR and immunohistochemistry. Transwell assays were conducted to examine the impact of ENPP3 overexpression on the migratory and invasive capabilities of endometrial stromal cells. Our results demonstrated significantly reduced methylation levels at the CpG sites of the ENPP3 promoter region in ectopic endometrial tissues compared to normal endometrial tissues. RT-qPCR findings revealed a marked increase in ENPP3 expression in ovarian EMs tissues relative to endometrial tissues from patients without EMs, and this upregulation was negatively correlated with the methylation levels of the ENPP3 promoter region. Immunohistochemical analyses confirmed elevated ENPP3 expression in the glandular epithelial cells and stroma of ovarian EMs tissues. Furthermore, in vitro experiments showed that overexpressed ENPP3 notably intensified the invasion and migration of endometrial stromal cells. Transcriptome sequencing and functional analyses indicated that the increased ENPP3 expression activated the AKT/mTOR/4EBP1 signaling pathway. In summary, the study suggests that hypomethylation in the ENPP3 promoter region may contribute to the initiation and advancement of ovarian EMs by activating the AKT/mTOR/4EBP1 pathway, supporting the theory that EMs might be an epigenetically regulated disorder.

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Hypomethylation of the ENPP3 promoter region contributes to the occurrence and development of ovarian endometriosis via the AKT/mTOR/4EBP1 signaling pathway

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Published

27-12-2023

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Research article

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How to Cite

1.
Hypomethylation of the ENPP3 promoter region contributes to the occurrence and development of ovarian endometriosis via the AKT/mTOR/4EBP1 signaling pathway. Biomol Biomed [Internet]. 2023 Dec. 27 [cited 2024 Dec. 11];24(4):848-56. Available from: https://bjbms.org/ojs/index.php/bjbms/article/view/9989