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Altered m6 A modification is involved in up-regulated expression of FOXO3 in luteinized granulosa cells of non-obese polycystic ovary syndrome patients.
Zhang, Shen; Deng, Wenli; Liu, Qiongyou; Wang, Peiyu; Yang, Wei; Ni, Wuhua.
Afiliación
  • Zhang S; Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Deng W; Department of Ophthalmology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China.
  • Liu Q; School of Basic Medical Sciences, Zunyi Medical University, Zunyi, China.
  • Wang P; Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • Yang W; The State Key Laboratory of Respiratory Disease, Guangdong Provincial Key Laboratory of Allergy & Clinical Immunology, The Second Affiliated Hospital, Guangzhou Medical University, Guangzhou, China.
  • Ni W; Reproductive Medicine Center, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
J Cell Mol Med ; 24(20): 11874-11882, 2020 10.
Article en En | MEDLINE | ID: mdl-32869942
The pathophysiology of polycystic ovary syndrome (PCOS) is characterized by granulosa cell (GC) dysfunction. m6 A modification affects GC function in patients with premature ovarian insufficiency (POI), but the role of m6 A modification in PCOS is unknown. The purpose of the prospective comparative study was to analyse the m6 A profile of the luteinized GCs from normovulatory women and non-obese PCOS patients following controlled ovarian hyperstimulation. RNA m6 A methylation levels were measured by m6 A quantification assay in the luteinized GCs of the controls and PCOS patients. Then, m6 A profiles were analysed by methylated RNA immunoprecipitation sequencing (MeRIP-seq). We reported that the m6 A level was increased in the luteinized GCs of PCOS patients. Comparative analysis revealed differences between the m6 A profiles from the luteinized GC of the controls and PCOS patients. We identified FOXO3 mRNA with reduced m6 A modification in the luteinized GCs of PCOS patients. Selectively knocking down m6 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 m6 A-mediated transcription of FOXO3 in the luteinized GCs of PCOS patients. Furthermore, we demonstrated that the involvement of m6 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 m6 A modification was involved in up-regulated expression of FOXO3 mRNA in the luteinized GCs from non-obese PCOS patients following controlled ovarian hyperstimulation.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Adenosina / Regulación hacia Arriba / Luteinización / Proteína Forkhead Box O3 / Células de la Granulosa Tipo de estudio: Observational_studies / Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Síndrome del Ovario Poliquístico / Adenosina / Regulación hacia Arriba / Luteinización / Proteína Forkhead Box O3 / Células de la Granulosa Tipo de estudio: Observational_studies / Prognostic_studies Límite: Adult / Female / Humans Idioma: En Revista: J Cell Mol Med Asunto de la revista: BIOLOGIA MOLECULAR Año: 2020 Tipo del documento: Article País de afiliación: China Pais de publicación: Reino Unido