Department of Neurobiology, Basic Medicine College, China Medical University, Shenyang, Liaoning, China.
Department of Neurosurgery, Shengjing Hospital, China Medical University, Shenyang, Liaoning, China.
Cancer Chemother Pharmacol. 2018 Apr;81(4):671-678. doi: 10.1007/s00280-018-3522-y. Epub 2018 Feb 3.
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.
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.
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.
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.
人多形性胶质母细胞瘤（GBM）是最恶性的颅内原发性癌症，与高死亡率和预后不良相关。本研究旨在探讨肿瘤抑制候选基因 7（TUSC7）对胶质瘤细胞恶性增殖和替莫唑胺（TMZ）化疗耐药的调控作用及其机制。
采用实时定量 PCR 检测 TUSC7 的表达。CCK-8 法检测细胞增殖能力和化疗敏感性。流式细胞术检测细胞周期和细胞凋亡。Western blot 检测多药耐药蛋白 1（MDR1）蛋白的表达。RNA 下拉实验证实 TUSC7 与 miR-10a 的特异性结合。
本研究检测到 TMZ 耐药的 GBM 细胞和组织中 TUSC7 表达下调。上调 TUSC7 抑制了 U87TR 细胞的 TMZ 耐药和多药耐药蛋白 1（MDR1）的表达。TUSC7 通过直接靶向和沉默 miR-10a 基因的表达，介导了 TUSC7 抑制 U87TR 细胞 TMZ 耐药的作用。
这些发现提示 TUSC7 表达与 TMZ 耐药呈负相关，并为针对 TUSC7 治疗 GBM 提供了机制和理论依据。
