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CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
骨髓间充质干细胞来源外泌体中的 LncRNA GHET1 通过介导 NLRP3 改善多柔比星诱导的心肌细胞焦亡
英文原题：LncRNA GHET1 from bone mesenchymal stem cell-derived exosomes improves doxorubicin-induced pyroptosis of cardiomyocytes by mediating NLRP3.
查看英文原题
LncRNA GHET1 from bone mesenchymal stem cell-derived exosomes improves doxorubicin-induced pyroptosis of cardiomyocytes by mediating NLRP3.
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中文摘要
多柔比星（DOX）是治疗血液系统肿瘤和乳腺癌的重要化疗药物。然而，由于其严重的心脏毒性，其临床应用受到限制。细胞焦亡是一种与DOX诱导的心脏毒性相关的程序性细胞死亡形式。骨髓间充质干细胞来源的外泌体（BMSC-Exos）和内皮祖细胞来源的外泌体（EPC-Exos）在心肌中具有保护作用。
本研究发现，BMSC-Exos可通过抑制细胞焦亡改善DOX诱导的心脏毒性，而EPC-Exos则不能。与EPC-Exo相比，过表达lncRNA GHET1的BMSC-Exo更有效地抑制细胞焦亡，从而对抗DOX诱导的心脏毒性。
进一步研究表明，lncRNA GHET1通过结合IGF2 mRNA结合蛋白1（IGF2BP1）有效降低Nod样受体蛋白3（NLRP3）的表达，NLRP3在细胞焦亡中发挥重要作用，而IGF2BP1是NLRP3 mRNA的非催化性转录后增强因子。
总之，BMSC-Exo释放的lncRNA GHET1通过靶向IGF2BP1减少NLRP3的转录后稳定性，从而改善DOX诱导的细胞焦亡。
展开英文摘要原文
Doxorubicin (DOX) is an important chemotherapeutic agent for the treatment of hematologic tumors and breast carcinoma.
However, its clinical application is limited owing to severe cardiotoxicity. Pyroptosis is a form of programmed cell death linked to DOX-induced cardiotoxicity. Bone mesenchymal stem cell-derived exosomes (BMSC-Exos) and endothelial progenitor cells-derived exosomes (EPC-Exos) have a protective role in the myocardium.
Here we found that BMSC-Exos could improve DOX-induced cardiotoxicity by inhibiting pyroptosis, but EPC-Exos couldn't. Compared with EPCs-Exo, BMSC-Exo-overexpressing lncRNA GHET1 more effectively suppressed pyroptosis, protecting against DOX-induced cardiotoxicity.
Further studies showed that lncRNA GHET1 effectively decreased the expression of Nod-like receptor protein 3 (NLRP3), which plays a vital role in pyroptosis by binding to IGF2 mRNA-binding protein 1 (IGF2BP1), a non-catalytic posttranscriptional enhancer of NLRP3 mRNA. In summary, lncRNA GHET1 released by BMSC-Exo ameliorated DOX-induced pyroptosis by targeting IGF2BP1 to reduce posttranscriptional stabilization of NLRP3.
论文信息
- 作者
- Zhai X、Zhou J、Huang X、Weng J、Lin H、Sun S、Chi J、Meng L
- 第一作者单位
- Department of Cardiology, Shaoxing People's Hospital, Shaoxing, China.China
- 通讯作者单位
- Department of Cardiology, Shaoxing People's Hospital, Shaoxing, China. mengliping@zju.edu.cn.China
- 期刊
- Scientific reports2024 Aug 17
- 原文标识
- PubMed 39154102 · DOI 10.1038/s41598-024-70151-w
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