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microRNA-181a mediates the chemo-sensitivity of glioblastoma to carmustine and regulates cell proliferation, migration, and apoptosis.

Authors :
Rezaei T
Hejazi M
Mansoori B
Mohammadi A
Amini M
Mosafer J
Rezaei S
Mokhtarzadeh A
Baradaran B
Source :
European journal of pharmacology [Eur J Pharmacol] 2020 Dec 05; Vol. 888, pp. 173483. Date of Electronic Publication: 2020 Aug 15.
Publication Year :
2020

Abstract

Glioblastoma multiform (GBM) as the most frequent and lethal brain tumor is defined by aggressive invasiveness and considerable resistance to chemotherapy. The molecular mechanisms underlying GBM tumorigenesis still needs to be further investigated. Considering that, the current study was aimed to investigate the function of miR-181a in human glioblastoma cells in combination with carmustine. U373 cell line with the low expression levels of miR-181a was selected for functional investigations. MTT assay was used to determine cell viability and Annexin V/PI and DAPI staining were employed to evaluate apoptosis induction. Also, cell migration and cell cycle progression were investigated using wound healing test and flow cytometry, respectively. qRT-PCR was used for the quantification of gene expression. MTT assay results revealed that miR-181a replacement increased the sensitivity of U373 cells to low doses of carmustine. Moreover, miR-181a was shown to increase the sub G1 cell cycle arrest and apoptosis induction by carmustine via regulating the expression of related genes including caspase-9, Bcl-2, and SIRT1. Furthermore, this miRNA combined with carmustine suppressed cell migration via downregulation of MMP-2 and Bach1 and reduced the clonogenic ability of U373 cells. Additionally, miR-181a-mediated downregulation of AKT1 implied that this miRNA could inhibit cell proliferation by modulating PI3K/AKT signaling pathway. In conclusion, the findings of this study suggest that miR-181a replacement, regarding its tumor-suppressive effects and sensitization of glioblastoma cells to carmustine, could be considered as a potential therapeutic strategy to improve the efficiency of glioblastoma chemotherapy.<br /> (Copyright © 2020 Elsevier B.V. All rights reserved.)

Details

Language :
English
ISSN :
1879-0712
Volume :
888
Database :
MEDLINE
Journal :
European journal of pharmacology
Publication Type :
Academic Journal
Accession number :
32810491
Full Text :
https://doi.org/10.1016/j.ejphar.2020.173483