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

in Cell biology and toxicology by Lichao Tang, Yutao Yang, Mingxin Yang, Jiaxin Xie, Aiping Zhuo, Yanhong Wu, Mengli Mao, Youhong Zheng, Xiafei Fu

TLDR

  • The study found that miR-21-Exo can mitigate chemotherapy-induced POI by regulating MALT1 and the NF-κB pathway, offering a potential therapeutic strategy for addressing this side effect.
  • Key Insights: The study provides a novel approach to addressing chemotherapy-induced POI by modulating MALT1 and the NF-κB pathway, highlighting the therapeutic potential and safety of miR-21-Exo.

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.

Overview

  • The study investigates the role of exosomes enriched with miR-21 (miR-21-Exo) in mitigating premature ovarian insufficiency (POI) induced by chemotherapy.
  • The study uses an experimental model where KGN cells are exposed to cisplatin and assesses the impact of miR-21 on cellular activity and the effects of miR-21-Exo.
  • The study aims to explore the underlying mechanisms of miR-21-Exo and its potential as a therapeutic strategy for addressing chemotherapy-induced POI.

Comparative Analysis & Findings

  • The study found that miR-21-Exo regulates Mucosa-Associated Lymphoid Tissue Lymphoma Translocation Protein 1 (MALT1) and the NF-κB signaling pathway, preventing cell pyroptosis.
  • The study identified MALT1 as a target of miR-21 using bioinformatics analysis.
  • The study demonstrated the therapeutic potential and safety of miR-21-Exo in a rat model.

Implications and Future Directions

  • The study provides a novel strategy for addressing chemotherapy-induced POI by modulating MALT1 and the NF-κB pathway.
  • Future studies can investigate the optimal dosage and delivery methods of miR-21-Exo for clinical application.
  • Further research can explore the potential of miR-21-Exo in treating other chemotherapy-induced side effects and improving patient outcomes.
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