MicroRNA-16 inhibits the growth and metastasis of human glioma cells via modulation of PI3K/AKT/mTOR signalling pathway

Abstract

IntroductionGliomas are lethal cancers accounting for significant human mortality across the globe. MicroRNAs (miRs) have shown potential to act as therapeutic targets for the treatment of cancer. Herein the role and therapeutic implications of miR-16 in glioma were investigated.Material and methodsExpression analysis was carried out by qRT-PCR. CellTiter-Glo assay (Promega) was used for the determination of cell proliferation. DAPI, AO/EB, and annexin V/PI assays were used to detect apoptosis. Wound healing and Transwell assays were used for cell migration and invasion, respectively. Western blot analysis was used for the determination of protein expression.ResultsThe study revealed that miR-16 was significantly suppressed in the human glioma cells. Ectopic expression of miR-16 in U118 MG cells inhibited the proliferation via induction of apoptosis. The apoptosis induction was also accompanied by an upsurge of Bax and depletion of Bcl-2. The overexpression of miR-16 also inhibited the migration and invasion of the glioma U118 MG cells, as evident from the wound healing and transwell assays, which were accompanied by the inhibition of metalloproteinase-2 and -9 (MMP-2 and MMP-9). The effects of miR-16 overexpression were also examined on the PI3K/AKT/mTOR signalling pathway. The results showed that miR-16 overexpression inhibited the phosphorylation of the p70S6K, AKT, and mTOR at Ser473, Ser2448, and Thr389, respectively, with no apparent effects on the total PI3K and AKT.ConclusionsmiR-16 acts as tumour suppressor in glioma and may severe as therapeutic target for glioma treatment.