Altered m6A modification is involved in up‐regulated expression of FOXO3 in luteinized granulosa cells of non‐obese polycystic ovary syndrome patients. Issue 20 (1st September 2020)

• Record Type: Journal Article
• Authors: Zhang, Shen; Deng, Wenli; Liu, Qiongyou; Wang, Peiyu; Yang, Wei; Ni, Wuhua
• Is Part Of: Journal of cellular and molecular medicine. Volume 24:Issue 20(2020)
• Page Start: 11874
• Page End: 11882
• Publication Date: 2020-09-01
• Subjects: FOXO3 -- luteinized granulosa cells -- mRNA decay -- N6‐methyladenosine -- polycystic ovary syndrome; Cytology; Medicine; Molecular Biology; Cytologie -- Périodiques; Médecine -- Périodiques; Biologie moléculaire -- Périodiques; Cytology -- Periodicals; Medicine -- Periodicals; Molecular biology -- Periodicals; 611.01805
• DOI: 10.1111/jcmm.15807
• Languages: English
• ISSNs: 1582-1838

Abstract

Abstract: The pathophysiology of polycystic ovary syndrome (PCOS) is characterized by granulosa cell (GC) dysfunction. m 6 A modification affects GC function in patients with premature ovarian insufficiency (POI), but the role of m 6 A modification in PCOS is unknown. The purpose of the prospective comparative study was to analyse the m 6 A profile of the luteinized GCs from normovulatory women and non‐obese PCOS patients following controlled ovarian hyperstimulation. RNA m 6 A methylation levels were measured by m 6 A quantification assay in the luteinized GCs of the controls and PCOS patients. Then, m 6 A profiles were analysed by methylated RNA immunoprecipitation sequencing (MeRIP‐seq). We reported that the m 6 A level was increased in the luteinized GCs of PCOS patients. Comparative analysis revealed differences between the m 6 A profiles from the luteinized GC of the controls and PCOS patients. We identified FOXO3 mRNA with reduced m 6 A modification in the luteinized GCs of PCOS patients. Selectively knocking down m 6 A methyltransferases or demethylases altered expression of FOXO3 in the luteinized GCs from the controls, but did not in PCOS patients. These suggested an absence of m 6 A‐mediated transcription of FOXO3 in the luteinized GCs of PCOS patients. Furthermore, we demonstrated that the involvement of m 6 A in the stability of the FOXO3 mRNA that is regulated via a putative methylation site in the 3'‐UTR only in the luteinized GCs of the controls. In summary, our findings showed that altered m 6 A modification was involved in up‐regulated expression of FOXO3 mRNA in the luteinized GCs from non‐obese PCOS patients following controlled ovarian hyperstimulation.