髓系白血病
癌症研究
骨髓
微泡
间充质干细胞
阿糖胞苷
Wnt信号通路
白血病
干细胞
外体
化学
髓样
医学
生物
信号转导
免疫学
小RNA
细胞生物学
生物化学
基因
作者
Juan Wu,Yaqin Zhang,Xiaoyü Li,Jingyi Ren,Ling Chen,Jiadi Chen,Yingping Cao
标识
DOI:10.1016/j.bbrc.2022.07.017
摘要
Bone marrow mesenchymal stem cells (BMSCs) are an integral part of the acute myeloid leukemia (AML) bone marrow microenvironment and contribute to AML progression. In this study, we explored the communication between BMSCs and AML cells via exosomes. The AML cells co-cultured with BMSCs-Exos were found to have lower chemosensitivity exposed to cytarabine, suggesting that BMSCs-Exos could protect AML cells from cytarabine. Interestingly, miR-10a was elevated in BMSCs-Exos derived from AML (AML-BMSCs-Exos) compared with that from healthy donor. The expression levels of miR-10a in AML cells was significantly up-regulated after co-culture with BMSCs-Exos. Furthermore, the up-regulated miR-10a was an crucial factor contributing to the chemoresistance of leukemia cells. Down-regulation of miR-10a substantially increase chemosensitivity of AML cells treated with BMSCs-Exos. Chemosensitivity of AML cells was also decreased through down-regulating RPRD1A by miR-10a that ultimately lead to the stimulation of the Wnt/β-catenin signaling pathway. Collectively, our findings demonstrated that AML-BMSCs could deliver miR-10a to AML cells via exosomes, which could target RPRD1A and activate Wnt/β-catenin signaling pathway that subsequently decreased chemosensitivity of AML cells.
科研通智能强力驱动
Strongly Powered by AbleSci AI