Exploring Diagnostic M6A Regulators in Endometriosis

Overview

Journal Aging (Albany NY)

Specialty Geriatrics

Date 2020 Nov 24

PMID 33232273

Citations 29

Authors

Li Jiang

Mengmeng Zhang

Jingni Wu

Sixue Wang

Xiang Yang

Mingyu Yi

Xinyue Zhang

Xiaoling Fang

Affiliations

Soon will be listed here.

Abstract

Endometriosis is an estrogen-dependent inflammatory disorder, usually causing infertility, pelvic pain, and ovarian masses. This study intended to investigate the implication of N6-methyladenosine (m6A) regulators in endometriosis. We acquired 34 normal, 127 eutopic, and 46 ectopic, samples of endometrium from the Gene Expression Omnibus (GSE7305, GSE7307, GSE51981) database and the Array-express (E-MTAB-694) database. These samples were then used to profile the expression of 20 m6A regulators in endometriosis. The results indicated that most dysregulated (19/20) m6A regulators were significantly downregulated in eutopic normal endometrium and also significantly downregulated in ectopic eutopic endometrium. Several dysregulated m6A regulators were common to both contrast matrices: METTL3, YTHDF2, YTHDF3, HNRNPA2B1, HNRNPC, and FTO. Both HNRNPA2B1 and HNRNPC were associated with the severity of endometriosis in eutopic samples, and also exhibited diagnostic potential for endometriosis. HNRNPA2B1 and HNRNPC may influence immune pathways and the infiltration of immune cells in endometriosis. Abnormalities in the gene transcription factors network associated with endometriosis might affect the expression of HNRNPA2B1 and HNRNPC. In conclusion, we observed significant dysregulation of m6A regulators in endometriosis, and found that HNRNPA2B1 and HNRNPC might correlate with the immune response and serve as useful diagnostic biomarkers for endometriosis.

Citing Articles

A novel mechanism of FTO modulating the progression of endometriosis through mediating the m6A methylation of GEF-H1 in a YTHDF1-dependent manner.

Ding X, Zhang H, Chen J, Yang M, Huang Z, Lei Y Mol Med. 2025; 31(1):78.

PMID: 40000966 PMC: 11863856. DOI: 10.1186/s10020-025-01130-8.

Epigenetic regulation in female reproduction: the impact of m6A on maternal-fetal health.

Li P, Lin Y, Ma H, Zhang J, Zhang Q, Yan R Cell Death Discov. 2025; 11(1):43.

PMID: 39904996 PMC: 11794895. DOI: 10.1038/s41420-025-02324-z.

Bioinformatic identification of important roles of COL1A1 and TNFRSF12A in cartilage injury and osteoporosis.

Liu M, Gong S, Sheng X, Zhang Z, Wang X J Int Soc Sports Nutr. 2025; 22(1):2454641.

PMID: 39847474 PMC: 11758804. DOI: 10.1080/15502783.2025.2454641.

N-Methyladenosine Modification on the Function of Female Reproductive Development and Related Diseases.

Cui X, Li H, Huang X, Xue T, Wang S, Zhu X Immun Inflamm Dis. 2024; 12(12):e70089.

PMID: 39660878 PMC: 11632877. DOI: 10.1002/iid3.70089.

Kidney fibrosis molecular mechanisms Spp1 influences fibroblast activity through transforming growth factor beta smad signaling.

Ding H, Xu Z, Lu Y, Yuan Q, Li J, Sun Q iScience. 2024; 27(9):109839.

PMID: 39323737 PMC: 11422156. DOI: 10.1016/j.isci.2024.109839.

References

Xu C, Liu K, Ahmed H, Loppnau P, Schapira M, Min J . Structural Basis for the Discriminative Recognition of N6-Methyladenosine RNA by the Human YT521-B Homology Domain Family of Proteins. J Biol Chem. 2015; 290(41):24902-13. PMC: 4598999. DOI: 10.1074/jbc.M115.680389. View

Aghajanova L, Giudice L . Molecular evidence for differences in endometrium in severe versus mild endometriosis. Reprod Sci. 2010; 18(3):229-51. PMC: 3118406. DOI: 10.1177/1933719110386241. View

Kim T, Yu Y, Luo L, Lydon J, Jeong J, Kim J . Activated AKT pathway promotes establishment of endometriosis. Endocrinology. 2014; 155(5):1921-30. PMC: 3990849. DOI: 10.1210/en.2013-1951. View

Yu G, Wang L, Han Y, He Q . clusterProfiler: an R package for comparing biological themes among gene clusters. OMICS. 2012; 16(5):284-7. PMC: 3339379. DOI: 10.1089/omi.2011.0118. View

Liang S, Guan H, Lin X, Li N, Geng F, Li J . METTL3 serves an oncogenic role in human ovarian cancer cells partially via the AKT signaling pathway. Oncol Lett. 2020; 19(4):3197-3204. PMC: 7074459. DOI: 10.3892/ol.2020.11425. View

Ritchie M, Phipson B, Wu D, Hu Y, Law C, Shi W . limma powers differential expression analyses for RNA-sequencing and microarray studies. Nucleic Acids Res. 2015; 43(7):e47. PMC: 4402510. DOI: 10.1093/nar/gkv007. View

Edupuganti R, Geiger S, Lindeboom R, Shi H, Hsu P, Lu Z . N-methyladenosine (mA) recruits and repels proteins to regulate mRNA homeostasis. Nat Struct Mol Biol. 2017; 24(10):870-878. PMC: 5725193. DOI: 10.1038/nsmb.3462. View

Gao Y, Pei G, Li D, Li R, Shao Y, Zhang Q . Multivalent mA motifs promote phase separation of YTHDF proteins. Cell Res. 2019; 29(9):767-769. PMC: 6796879. DOI: 10.1038/s41422-019-0210-3. View

Shi H, Wang X, Lu Z, Zhao B, Ma H, Hsu P . YTHDF3 facilitates translation and decay of N-methyladenosine-modified RNA. Cell Res. 2017; 27(3):315-328. PMC: 5339834. DOI: 10.1038/cr.2017.15. View

10.

Zheng G, Dahl J, Niu Y, Fedorcsak P, Huang C, Li C . ALKBH5 is a mammalian RNA demethylase that impacts RNA metabolism and mouse fertility. Mol Cell. 2012; 49(1):18-29. PMC: 3646334. DOI: 10.1016/j.molcel.2012.10.015. View

11.

Hanzelmann S, Castelo R, Guinney J . GSVA: gene set variation analysis for microarray and RNA-seq data. BMC Bioinformatics. 2013; 14:7. PMC: 3618321. DOI: 10.1186/1471-2105-14-7. View

12.

Zhu Y, Shen J, Gao L, Feng Y . Estrogen promotes fat mass and obesity-associated protein nuclear localization and enhances endometrial cancer cell proliferation via the mTOR signaling pathway. Oncol Rep. 2016; 35(4):2391-7. DOI: 10.3892/or.2016.4613. View

13.

Zhao Y, Tao Z, Chen X . Identification of a three-m6A related gene risk score model as a potential prognostic biomarker in clear cell renal cell carcinoma. PeerJ. 2020; 8:e8827. PMC: 7085294. DOI: 10.7717/peerj.8827. View

14.

Vallve-Juanico J, Houshdaran S, Giudice L . The endometrial immune environment of women with endometriosis. Hum Reprod Update. 2019; 25(5):564-591. PMC: 6737540. DOI: 10.1093/humupd/dmz018. View

15.

Bulun S, Monsavais D, Pavone M, Dyson M, Xue Q, Attar E . Role of estrogen receptor-β in endometriosis. Semin Reprod Med. 2012; 30(1):39-45. PMC: 4034571. DOI: 10.1055/s-0031-1299596. View

16.

Liu J, Eckert M, Harada B, Liu S, Lu Z, Yu K . mA mRNA methylation regulates AKT activity to promote the proliferation and tumorigenicity of endometrial cancer. Nat Cell Biol. 2018; 20(9):1074-1083. PMC: 6245953. DOI: 10.1038/s41556-018-0174-4. View

17.

Burney R, Talbi S, Hamilton A, Vo K, Nyegaard M, Nezhat C . Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis. Endocrinology. 2007; 148(8):3814-26. DOI: 10.1210/en.2006-1692. View

18.

Hever A, Roth R, Hevezi P, Marin M, Acosta J, Acosta H . Human endometriosis is associated with plasma cells and overexpression of B lymphocyte stimulator. Proc Natl Acad Sci U S A. 2007; 104(30):12451-6. PMC: 1941489. DOI: 10.1073/pnas.0703451104. View

19.

Wang H, Xu B, Shi J . N6-methyladenosine METTL3 promotes the breast cancer progression via targeting Bcl-2. Gene. 2019; 722:144076. DOI: 10.1016/j.gene.2019.144076. View

20.

Amirteimouri S, Ashini M, Ramazanali F, Aflatoonian R, Afsharian P, Shahhoseini M . Epigenetic role of the nuclear factor NF-Y on ID gene family in endometrial tissues of women with endometriosis: a case control study. Reprod Biol Endocrinol. 2019; 17(1):32. PMC: 6419829. DOI: 10.1186/s12958-019-0476-9. View