EIF4A3-Induced Exosomal circLRRC8A Alleviates Granulosa Cells Senescence Via the miR-125a-3p/NFE2L1 axis

• DOI: 10.1007/s12015-023-10564-8
• Publication Date: 2023-05-27T09:02:32Z
• Authors: Jie Xing; Mengxue Zhang; Shijie Zhao; Mingjun Lu; Li Lin; Lu Chen; Wujiang Gao; Wenxin Li; Junyu Shang; Jiamin Zhou; Xiaolan Zhu
• Keywords: Senescence; Exosome

Abstract Premature ovarian failure (POF) is an important cause of female infertility and seriously impacts the physical psychological health patients. Mesenchymal stromal cells-derived exosomes (MSCs-Exos) have essential role in treatment reproductive disorders, particularly POF. However, biological function therapeutic mechanism MSCs exosomal circRNAs POF remain to be determined. Here, with bioinformatics analysis functional assays, circLRRC8A was found downregulated senescent granulosa cells (GCs) acted as a crucial factor MSCs-Exos for oxidative damage protection anti-senescence GCs vitro vivo. Mechanistic investigations revealed that served endogenous miR-125a-3p sponge downregulate NFE2L1 expression. Moreover, eukaryotic initiation 4A3 (EIF4A3), acting pre-mRNA splicing factor, promoted cyclization expression by directly binding LRRC8A mRNA transcript. Notably, EIF4A3 silencing reduced attenuated effect on oxidatively damaged GCs. This study demonstrates new pathway cellular senescence against delivering circLRRC8A-enriched through circLRRC8A/miR-125a-3p/NFE2L1 axis paves way establishment cell-free approach CircLRRC8A may promising circulating biomarker diagnosis prognosis exceptional candidate further exploration. Graphical