Decreased miR-128-3p in serum exosomes from polycystic ovary syndrome induces ferroptosis in granulosa cells via the p38/JNK/SLC7A11 axis through targeting CSF1.

ABSTRACT: Increasing evidence suggests that non-coding small RNAs (miRNAs) carried by exosomes (EXOs) play important roles in the development and treatment of polycystic ovary syndrome (PCOS). In this study, we demonstrate that PCOS mouse serum-derived EXOs promote granulosa cells (GCs) ferroptosis, and induce the occurrence of a PCOS-like phenotype in vivo. Notably, EXO miRNA sequencing combined with in vitro gain- and loss-of-function assays revealed that miR-128-3p, which is absent in the serum-derived EXOs of mice with PCOS, regulates lipid peroxidation and GC sensitivity to ferroptosis inducers. Mechanistically, overexpression of CSF1, a direct target of miR-128-3p, reversed the anti-ferroptotic effect of miR-128-3p. Conversely, ferroptosis induction was mitigated in CSF1-downregulated GCs. Fur

SUBMITTER: Lv Y 

PROVIDER: S-EPMC11836375 | biostudies-literature | 2025 Feb

REPOSITORIES: biostudies-literature