Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2021 May;34(3):965-976.
doi: 10.1007/s13577-021-00501-7. Epub 2021 Feb 23.

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

Dexiang Ji #  1 , Yue He #  1 , Wei Lu  1 , Yanyan Rong  1 , Fei Li  1 , Xianbao Huang  1 , Ruibin Huang  1 , Yanxia Jiang  2 , Guoan Chen  3
Affiliations

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

Dexiang Ji et al. Hum Cell. 2021 May.

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.

PubMed Disclaimer

References

    1. De Kouchkovsky I, Abdul-Hay M. Acute myeloid leukemia: a comprehensive review and 2016 update. Blood Cancer J. 2016;6(7):e441. https://doi.org/10.1038/bcj.2016.50 . - DOI - PubMed - PMC
    1. Ferrara F, Palmieri S, Mele G. Prognostic factors and therapeutic options for relapsed or refractory acute myeloid leukemia. Haematologica. 2004;89(8):998–1008. - PubMed
    1. Galipeau J, Sensébé L. Mesenchymal stromal cells: clinical challenges and therapeutic opportunities. Cell Stem Cell. 2018;22(6):824–33. https://doi.org/10.1016/j.stem.2018.05.004 . - DOI - PubMed - PMC
    1. Fajardo-Orduña GR, Mayani H, Montesinos JJ. Hematopoietic support capacity of mesenchymal stem cells: biology and clinical potential. Arch Med Res. 2015;46(8):589–96. https://doi.org/10.1016/j.arcmed.2015.10.001 . - DOI - PubMed
    1. Low JH, Ramdas P, Radhakrishnan AK. Modulatory effects of mesenchymal stem cells on leucocytes and leukemic cells: a double-edged sword? Blood Cells Mol Dis. 2015;55(4):351–7. https://doi.org/10.1016/j.bcmd.2015.07.017 . - DOI - PubMed

MeSH terms

LinkOut - more resources