{"title":"hnRNPA2B1 restrains granulosa cell ferroptosis by m<sup>6</sup>A/SLC7A11 in premature ovarian failure.","authors":"Jing Xiong, Ling He, Yongjing Zhang, Xing Zhao","doi":"10.1186/s13048-025-01718-y","DOIUrl":null,"url":null,"abstract":"<p><p>Premature ovarian failure (POF) is a relatively severe gynecological disorder that is often accompanied by other systemic diseases. Here, this study identified that N<sup>6</sup>-methyladenosine (m<sup>6</sup>A) key enzyme heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) was associated with POF pathophysiological process. In the chemotherapy induced POF animal and cells, hnRNPA2B1 was down-regulated upon cisplatin (CDDP) treatment. Functionally, hnRNPA2B1 inhibited the ferroptosis phenotype by m<sup>6</sup>A/SLC7A11 of granulosa cells. Moreover, hnRNPA2B1 up-regulated the autophagy by inhibiting PI3K/AKT/mTOR pathway of granulosa cells. Besides, rescue experiments confirmed that hnRNPA2B1/SLC7A11 axis repressed the ferroptosis of granulosa cells through m<sup>6</sup>A-dependent manner. In summary, the research identified the critical role of hnRNPA2B1 in granulosa cells ferroptosis, which provides novel insight for POF treatment.</p>","PeriodicalId":16610,"journal":{"name":"Journal of Ovarian Research","volume":"18 1","pages":"165"},"PeriodicalIF":4.2000,"publicationDate":"2025-07-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12297619/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Ovarian Research","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1186/s13048-025-01718-y","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"REPRODUCTIVE BIOLOGY","Score":null,"Total":0}
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Abstract
Premature ovarian failure (POF) is a relatively severe gynecological disorder that is often accompanied by other systemic diseases. Here, this study identified that N6-methyladenosine (m6A) key enzyme heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) was associated with POF pathophysiological process. In the chemotherapy induced POF animal and cells, hnRNPA2B1 was down-regulated upon cisplatin (CDDP) treatment. Functionally, hnRNPA2B1 inhibited the ferroptosis phenotype by m6A/SLC7A11 of granulosa cells. Moreover, hnRNPA2B1 up-regulated the autophagy by inhibiting PI3K/AKT/mTOR pathway of granulosa cells. Besides, rescue experiments confirmed that hnRNPA2B1/SLC7A11 axis repressed the ferroptosis of granulosa cells through m6A-dependent manner. In summary, the research identified the critical role of hnRNPA2B1 in granulosa cells ferroptosis, which provides novel insight for POF treatment.
期刊介绍：
Journal of Ovarian Research is an open access, peer reviewed, online journal that aims to provide a forum for high-quality basic and clinical research on ovarian function, abnormalities, and cancer. The journal focuses on research that provides new insights into ovarian functions as well as prevention and treatment of diseases afflicting the organ.
Topical areas include, but are not restricted to:
Ovary development, hormone secretion and regulation
Follicle growth and ovulation
Infertility and Polycystic ovarian syndrome
Regulation of pituitary and other biological functions by ovarian hormones
Ovarian cancer, its prevention, diagnosis and treatment
Drug development and screening
Role of stem cells in ovary development and function.
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