细胞外小泡
髓系白血病
小泡
细胞外
癌症研究
白血病
细胞生物学
髓样
微泡
化学
生物
小RNA
免疫学
生物化学
基因
膜
作者
Mengyu Li,Guohuan Sun,Jian Zhao,Shuangshuang Pu,Lv Y,Yifei Wang,Yapu Li,Xiangnan Zhao,Yajie Wang,Shangda Yang,Cheng Tien,Hui Cheng
标识
DOI:10.3324/haematol.2023.284145
摘要
Small extracellular vesicles (sEVs) transfer cargos between cells and participate in various physiological and pathological processes through their autocrine and paracrine effects. However, the pathological mechanisms employed by sEV-encapsulated microRNAs (miRNAs) in acute myeloid leukemia (AML) are still obscure. In this study, we aimed to investigate the effects of AML cells-derived sEVs (AML-sEVs) on AML cells and delineate the underlying mechanisms. We initially used high-throughput sequencing to identify miR-221-3p as the miRNA prominently enriched in AML-sEVs. Our findings revealed that miR-221-3p promoted AML cell proliferation and leukemogenesis by accelerating cell cycle entry and inhibiting apoptosis. Furthermore, Gbp2 was confirmed as a target gene of miR-221-3p by dual luciferase reporter assays and rescue experiments. Additionally, AML-sEVs impaired the clonogenicity, particularly the erythroid differentiation ability, of hematopoietic stem and progenitor cells. Taken together, our findings reveal how sEVs-delivered miRNAs contribute to AML pathogenesis, which can be exploited as a potential therapeutic target to attenuate AML progression.
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