Regulation of mTOR by miR-107 to facilitate glioma cell apoptosis and to enhance cisplatin sensitivity

P.-F. Su, S.-Q. Song

Department of Neurosurgery, The Fifth Affiliated Hospital of Harbin Medical University, Daqing, Heilongjiang, China. xiapo22404@163.com

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• Oncology

OBJECTIVE: The aberrant increasing expression of mammalian target of rapamycin (mTOR) participates in tumor occurrence and drug resistance. It has been found elevation of mTOR expression but reducing miR-107 expression in glioma tissues. Thus, we investigated the regulatory role of miR-107 on mTOR expression as well as glioma cell proliferation, apoptosis and cisplatin (DDP) resistance.

PATIENTS AND METHODS: Dual luciferase reporter gene assay was applied to confirm targeted regulation between miR-107 and mTOR. Tumor tissues were collected from glioma patients, in parallel with normal tissues after brain contusion surgery. Expressions of miR-107, mTOR and p-mTOR were compared. DDP-resistant cell line U251/DPP was generated. U251/DPP cells were further treated with miR-107 mimic or si-mTOR to examine the change of miR-107, mTOR, p-mTOR and survivin levels. Flow cytometry was used to quantify the effect of DDP treatment on cell proliferation or apoptosis.

RESULTS: Bioinformatics analysis revealed complementary binding sites between miR-107 and 3’-UTR of mTOR mRNA. Dual luciferase assay confirmed targeted regulation between miR-107 and mTOR. Compared to control group, in glioma tissues, mTOR and p-mTOR expressions were significantly elevated, while the level of miR-107 expression was markedly decreased. Of note, U251/DDP cells presented weakened apoptosis compared to U251 cells, with high levels of mTOR, p-mTOR and survivin and reduction of miR-107 expression. However, the transfection of miR-107 mimic and/or si-mTOR remarkably suppressed expressions of mTOR, p-mTOR and survivin in U251/DPP cells, weakened cell proliferation and enhanced apoptosis.

CONCLUSIONS: We demonstrated that the level of miR-107 was correlated with DDP resistance in glioma cells. Over-expression of miR-107 decreased DPP resistance of glioma cells via inhibition of mTOR, which provides academic basis for the future anti-glioma therapy.

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