Department of Hematology, The First Affiliated Hospital of Nanchang University, No. 17 Yongwaizheng Street, Donghu District, Nanchang, 33000, Jiangxi, China.
Department of Endocrinology, The First Affiliated Hospital of Nanchang University, Nanchang, 33000, Jiangxi, China.
Hum Cell. 2021 May;34(3):965-976. doi: 10.1007/s13577-021-00501-7. Epub 2021 Feb 23.
Bone marrow mesenchymal stem cells (BMSCs) in acute myeloid leukemia (AML) microenvironment undergo modification that includes expression of contents in the small-sized extracellular vesicles (EVs) they secrete. This study aims to investigate whether small-sized EVs from BMSCs of AML patients regulate AML progression by modifying the expression of miR-26a-5p. Small-sized EVs from BMSCs of AML patients (AML-BMSC-EVs) or healthy controls (HC-BMSC-EVs) were isolated by ultra-centrifugation and administered to AML cells (OCI/AML-2 and THP-1). Cell proliferation, migration, and invasion were evaluated by CCK-8 assay, Transwell migration and invasion assays, respectively. Compared with HC-BMSC-EVs, AML-BMSC-EVs contained higher expression of miR-26a-5p and promoted AML cell proliferation, migration, and invasion. Inhibition of miR-26a-5p expression in AML-BMSC-EVs could abrogate the promoting effects of AML-BMSC-EVs on AML cell proliferation, migration, and invasion. Furthermore, GSK3β was a direct target of miR-26a-5p. Moreover, AML-BMSC-EVs inhibited GSK3β expression and activated Wnt/β-catenin signaling in AML cells. Additionally, GSK3β overexpression in THP-1 cells counteracted the promoting effects of AML-BMSCs-EVs on THP-1 cell proliferation, migration, and invasion. AML-BMSC-EVs promoted AML progression by transferring miR-26a-5p to AML cells and subsequently activating the Wnt/β-catenin pathway.
急性髓系白血病(AML)微环境中的骨髓间充质干细胞(BMSCs)经历了修饰,包括它们分泌的小细胞外囊泡(EVs)中的内容物的表达。本研究旨在探讨来自 AML 患者 BMSCs 的小 EV 是否通过修饰 miR-26a-5p 的表达来调节 AML 的进展。通过超速离心从 AML 患者(AML-BMSC-EVs)或健康对照(HC-BMSC-EVs)的 BMSCs 中分离小 EV,并将其给予 AML 细胞(OCI/AML-2 和 THP-1)。通过 CCK-8 测定、Transwell 迁移和侵袭测定分别评估细胞增殖、迁移和侵袭。与 HC-BMSC-EVs 相比,AML-BMSC-EVs 中 miR-26a-5p 的表达更高,并促进了 AML 细胞的增殖、迁移和侵袭。在 AML-BMSC-EVs 中抑制 miR-26a-5p 的表达可消除 AML-BMSC-EVs 对 AML 细胞增殖、迁移和侵袭的促进作用。此外,GSK3β 是 miR-26a-5p 的直接靶标。此外,AML-BMSC-EVs 在 AML 细胞中抑制 GSK3β 表达并激活 Wnt/β-catenin 信号通路。此外,在 THP-1 细胞中过表达 GSK3β 可抵消 AML-BMSCs-EVs 对 THP-1 细胞增殖、迁移和侵袭的促进作用。AML-BMSC-EVs 通过将 miR-26a-5p 转移至 AML 细胞并随后激活 Wnt/β-catenin 通路来促进 AML 的进展。
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