miR-21-loaded bone marrow mesenchymal stem cell-derived exosomes inhibit pyroptosis by targeting MALT1 to repair chemotherapy-induced premature ovarian insufficiency

载 miR-21 的骨髓间充质干细胞来源的外泌体通过靶向 MALT1 抑制细胞焦亡,从而修复化疗引起的卵巢功能不全

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作者:Lichao Tang, Yutao Yang, Mingxin Yang, Jiaxin Xie, Aiping Zhuo, Yanhong Wu, Mengli Mao, Youhong Zheng, Xiafei Fu

Abstract

Chemotherapy is essential for treating malignant tumors, but it can cause premature ovarian insufficiency (POI). Recent studies suggest that exosomes enriched with miR-21 (miR-21-Exo) may help mitigate POI, though the underlying mechanisms remain largely unexplored. This research investigates how miR-21-Exo influences chemotherapy-induced POI using an experimental model where KGN cells are exposed to cisplatin. We assessed the impact of miR-21 on cellular activity and generated miR-21 overexpressing bone marrow mesenchymal stem cells (miR-21-BMSC) via lentiviral modification. Isolated miR-21-Exo was analyzed for its effects on cellular function. Bioinformatics identified Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT1) as a target of miR-21. We confirmed that miR-21-Exo regulates MALT1 and the NF-κB signaling pathway to prevent cell pyroptosis. Further studies in a rat model demonstrated the therapeutic potential and safety of miR-21-Exo. Overall, our findings highlight a novel strategy for addressing chemotherapy-induced POI by modulating MALT1 and the NF-κB pathway, offering significant therapeutic implications.

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