| Glioblastoma multiform (GBM) as the most frequent and lethal brain tumor is defned 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 quantifcation 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-181amediated downregulation of AKT1 implied that this miRNA could inhibit cell proliferation by modulating PI3K/
AKT signaling pathway. In conclusion, the fndings 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 effciency of glioblastoma chemotherapy. |