Small-sized extracellular vesicles (EVs) derived from acute myeloid leukemia bone marrow mesenchymal stem cells transfer miR-26a-5p to promote acute myeloid leukemia cell proliferation, migration, and invasion

Abstract

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.

Keywords: Acute myeloid leukemia; GSK3β; Mesenchymal stem cells; Small-sized EVs; miR-26a-5p.