Abstract
ObjectiveTo investigate how serum extracellular vesicles (EVs)-carried miRNA-181b-5p affected the proliferation, cell cycle and apoptosis of acute lymphoblastic leukemia (ALL) cells.MethodsDifferentially expressed miRNAs related to ALL were screened by bioinformatics analysis, and the localization of target miRNA was searched by its expression. qRT-PCR was adopted to confirm the expression of miRNA-181b-5p. Flow cytometry and fluorescence microscopy were applied to evaluate EVs internalization. MTT assay was employed to verify the proliferation of ALL cells. Cell cycle and apoptosis were analyzed by flow cytometry. Transwell assay was applied to evaluate migration and invasion abilities.ResultsHigh expression of miRNA-181b-5p was proved in ALL cell lines, and miRNA-181b-5p enriched in the exosomes and vesicles of blood cells. In the meantime, it was found that EVs carrying miRNA-181b-5p could be internalized by ALL cells and thus the expression of miRNA-181b-5p was up-regulated. Cell function assays showed that the proliferation, migration, invasion abilities of ALL cell lines were promoted in miRNA-181b-5p mimic group or the group co-culturing ALL-derived EVs and BALL-1 cell lines. The percentage of cells in G0/G1 phase was reduced and cell apoptosis was also inhibited.ConclusionmiRNA-181b-5p carried by EVs in peripheral blood of ALL patients can enter ALL cells and thus promote the malignancy of ALL cells.
Highlights
Acute lymphoblastic leukemia (ALL) is a kind of tumor derived from the abnormal proliferation of B-lymphoblasts or T-lymphoblasts in the bone marrow
Li et al found that 182 miRNAs and 166 miRNAs were differentially expressed in Nalm-6-MVs and Jurkat-MVs respectively, and these abnormally expressed miRNAs target a variety of oncogenes, tumor suppressor genes and signaling pathway genes, which may be involved in the progression of B-ALL or T-ALL [16]
MiRNA‐181b‐5p regulates the proliferation, apoptosis and cycle of ALL cells To furtherly understand the impacts of miRNA-181b-5p on the biological functions of ALL cells, miRNA-181b-5p mimic, mimic NC, miRNA-181b-5p inhibitor, and
Summary
Acute lymphoblastic leukemia (ALL) is a kind of tumor derived from the abnormal proliferation of B-lymphoblasts or T-lymphoblasts in the bone marrow. The overall survival (OS) rate of adult patients who underwent allogeneic hematopoietic stem cell transplantation could be increased from 15–45% to 27–65%. Exosomes and micro-vesicles (MVs) are two major subtypes of EVs [9, 10] that are produced by healthy cells or cancer cells and can be detected in multiple body fluids, Yan et al Journal of Translational Medicine (2021) 19:511 such as blood, urine or saliva [8]. Several studies reported that EVs derived from cancer cells relate to microRNA (miRNA) enrichment in biological fluids of patients with cancers, suggesting that miRNA may be a marker to predict the prognosis of cancer [14, 15].
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