m6A methyltransferase METTL3 inhibits endometriosis by regulating alternative splicing of MIR17HG

in Reproduction
Authors:
Qian Li Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University and Henan Province Women and Children's Hospital, Zhengzhou, China

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Li Yang Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University and Henan Province Women and Children's Hospital, Zhengzhou, China

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Feng Zhang Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University and Henan Province Women and Children's Hospital, Zhengzhou, China

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Jiaxi Liu Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University and Henan Province Women and Children's Hospital, Zhengzhou, China

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Min Jiang Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University and Henan Province Women and Children's Hospital, Zhengzhou, China

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Yannan Chen Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University and Henan Province Women and Children's Hospital, Zhengzhou, China

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https://orcid.org/0000-0002-2779-3544
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Chenchen Ren Department of Gynecology, The Third Affiliated Hospital of Zhengzhou University and Henan Province Women and Children's Hospital, Zhengzhou, China

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Correspondence should be addressed to Y Chen or C Ren; Email: chenyannan@zzu.edu.cn or renchenchen1106@126.com
DOI:
https://doi.org/10.1530/REP-22-0102
Volume/Issue:
Volume 165: Issue 2
Page Range:
197–208
Article Type:
Research Article
Online Publication Date:
06 Jan 2023
Copyright:
© Society for Reproduction and Fertility 2023
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In brief

Inflammation and abnormal immune response are the key processes in the development of endometriosis (EMs), and m6A modification can regulate the inflammatory response. This study reveals that METTL3-mediated N6-methyladenosine (m6A) modification plays an important role in EMs.

Abstract

m6A modification is largely involved in the development of different diseases. This study intended to investigate the implication of m6A methylation transferase methyltransferase like 3 (METTL3) in EMs. EMs- and m6A-related mRNAs and long non-coding RNAs were identified through bioinformatics analysis. Next, EM mouse models established by endometrial autotransplantation and mouse endometrial stromal cell (mESC) were prepared and treated with oe-METTL3 or sh-MIR17HG for pinpointing the in vitro and in vivo effects of METTL3 on EMs in relation to MIR17HG through the determination of mESC biological processes as well as estradiol (E2) and related lipoprotein levels. We demonstrated that METTL3 and MIR17HG were downregulated in the EMs mouse model. Overexpression of METTL3 suppressed the proliferation, migration, and invasion of mESCs. In addition, METTL3 enhanced the expression of MIR17HG through m6A modification. Moreover, METTL3 could inhibit the E2 level and alter related lipoprotein levels in EMs mice through the upregulation of MIR17HG. The present study highlighted that the m6A methylation transferase METTL3 prevents EMs progression by upregulating MIR17HG expression.

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Print ISSN:
1470-1626
Online ISSN:
1741-7899

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