Purpose: Human glioblastoma multiforme (GBM) is the most malignant intracranial primary cancer and is associated with high mortality and poor prognosis. This study aimed to investigate the regulatory effects and mechanism of tumor suppressor candidate 7 (TUSC7) gene to malignant proliferation and chemotherapy resistance to temozolomide (TMZ) in glioma cells.
Methods: The expression of TUSC7 was detected by quantitative real-time PCR. CCK-8 assay was used to detect cell proliferation ability and chemosensitivity. Flow cytometry were used to detect cell cycle and cell apoptosis. The expression of MDR1 protein was examined by western blot. RNA pull-down assay was applied to confirm the specific combination between TUSC7 and miR-10a.
Results: In the present study, we detected low expression of TUSC7 in GBM cells and tissues resistant to TMZ. Upregulation of TUSC7 suppressed both TMZ resistance and expression of multidrug resistance protein 1 (MDR1) in U87TR cells. TUSC7 acted by directly targeting and silencing expression of miR-10a gene, and miR-10a mediated TUSC7-induced inhibition on TMZ resistance in U87TR cells.
Conclusions: These findings suggest a negative correlation between TUSC7 expression and TMZ resistance and provide a mechanism and rationale for targeting TUSC7 in the treatment of GBM.
Keywords: Chemotherapy; Glioblastoma multiforme; MicroRNA-10a; Non-coding RNA; Resistance; Temozolomide; Tumor suppressor candidate 7.