Abstract
Glioblastoma (GBM) is the most common malignant primary tumor in the human central nervous system. The present study aimed to explore the molecular mechanism by which microRNA (miR)-181a-5p targets the F-box protein 11 (FBXO11) in glioma cells to inhibit cell proliferation and invasion. Reverse transcription-quantitative (RT-q)PCR was performed to detect the expression levels of miR-181a-5p in U251TR cells, U251 cells, primary GBM tissues and relapsed GBM tissues in order to determine the association between miR-181a-5p and the chemoresistance of GBM cells. The expression levels of miR-181a-5p in GBM cells were modulated via transfecting miR-181a-5p mimics and inhibitors. Cell Counting Kit-8 assays were undertaken to assess the effects of miR-181a-5p on drug sensitivity and proliferation of GBM cells. Wound healing assays were performed to examine the effects of miR-181a-5p on the migratory ability of GBM cells. Furthermore, the effects of miR-181a-5p on the invasive ability of GBM cells were analyzed using an in vitro invasion assay. Flow cytometry analysis was carried out to determine whether overexpression of miR-181a-5p can promote the apoptotic rate of GBM cells. RT-qPCR and western blotting were employed to detect the effects of miR-181a-5p on mRNA and protein expression of FBX011. miR-181a-5p exhibited low expression in resistant GBM cell lines and recurrent tumor tissues. Dual-luciferase reporter assays were utilized to detect luciferase activity to verify the targeted regulatory association between miR-181a-5p and FBXO11. Upregulation of miR-181a-5p promoted the sensitivity of GBM cells to temozolomide (TMZ), increased the apoptotic rate of GBM cells and significantly inhibited the invasive and migratory capacities of GBM cells. In drug-resistant glioma cells, compared with the miR-negative control group and the blank group, the expression of miR-181a-5p was significantly upregulated (P<0.01), while the expression of FBXO11 protein was downregulated. miR-181a-5p increased the sensitivity of GBM cells to TMZ. miR-181a-5p significantly inhibited the migratory and invasive capacities of GBM cells. miR-181a-5p may become a novel effective target for the treatment of GBM. The results of dual-luciferase reporter assays indicated that miR-181a-5p could target the 3'-untranslated region of FBXO11. The underlying mechanism may be targeted inhibition of FBXO11 gene expression, or may be associated with apoptosis.