hnRNPA2B1 restrains granulosa cell ferroptosis by m6A/SLC7A11 in premature ovarian failure

Abstract

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.

Keywords

• Premature ovarian failure
• hnRNPA2B1
• SLC7A11
• Ferroptosis.