The delivery of hsa-miR-11401 by extracellular vesicles can relieve doxorubicin-induced mesenchymal stem cell apoptosis.

The delivery of hsa-miR-11401 by extracellular vesicles can relieve doxorubicin-induced mesenchymal stem cell apoptosis.
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细胞外囊泡递送 hsa-miR-11401 可减轻阿霉素诱导的间充质干细胞凋亡

DOI:
10.1186/s13287-021-02156-5
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发表时间:
2021-01-22
影响因子:
7.5
通讯作者:
Li Z
Li Z
中科院分区:
医学2区
文献类型:
--
作者:
Li H;Huang H;Chen X;Chen S;Yu L;Wang C;Liu Y;Zhang K;Wu L;Han ZC;Liu N;Wu J;Li Z

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研究背景化疗是一种有效的抗肿瘤治疗方法。间充质干细胞(MSC)在化疗过程中对受损组织发挥治疗作用,但在此过程中可能会受到损伤。通过远距离旁分泌实现自愈的可能性及其机制尚不清楚。方法用常用化疗药物阿霉素治疗人脐带间充质干细胞(hUC-MSCs)6小时作为化疗损伤的体外细胞模型。然后,我们使用胎盘间充质干细胞 (hP-MSC) 来源的细胞外囊泡来研究 MSC-EV 对化疗损伤的治疗潜力。利用microRNA测序探讨其机制。结果MSC来源的细胞外囊泡显着减轻化疗诱导的细胞凋亡。通过 microRNA 测序,我们鉴定了 hsa-miR-11401,它在 Dox 组中下调,但在 EV 组中上调。 hsa-miR-11401的上调可降低SCOTIN的表达,从而抑制p53依赖性细胞凋亡。结论MSCs表达的Hsa-miR-11401可以通过EVs转运至化疗损伤细胞,降低受损细胞中SCOTIN的高表达,从而抑制SCOTIN介导的细胞凋亡。
BackgroundChemotherapy is an effective anti-tumor treatment. Mesenchymal stem cells (MSCs), exerting therapy effect on injured tissues during chemotherapy, may be damaged in the process. The possibility of self-healing through long-range paracrine and the mechanisms are unclear.MethodsDoxorubicin, a commonly used chemotherapy drug, was to treat human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) for 6 h as an in vitro cell model of chemotherapy-induced damage. Then we use extracellular vesicles derived from placental mesenchymal stem cells (hP-MSCs) to investigate the therapeutic potential of MSCs-EVs for chemotherapy injury. The mechanism was explored using microRNA sequencing.ResultsMSC-derived extracellular vesicles significantly alleviated the chemotherapy-induced apoptosis. Using microRNA sequencing, we identified hsa-miR-11401, which was downregulated in the Dox group but upregulated in the EV group. The upregulation of hsa-miR-11401 reduced the expression of SCOTIN, thereby inhibiting p53-dependent cell apoptosis.ConclusionsHsa-miR-11401 expressed by MSCs can be transported to chemotherapy-damaged cells by EVs, reducing the high expression of SCOTIN in damaged cells, thereby inhibiting SCOTIN-mediated apoptosis.
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