Department of Oncology, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China.
Department of Neurosurgery, The Third People's Hospital of Linyi, Linyi, Shandong 276023, P.R. China.
Mol Med Rep. 2018 Nov;18(5):4747-4752. doi: 10.3892/mmr.2018.9458. Epub 2018 Sep 5.
Cisplatin, a commonly used chemotherapeutic agent for glioma patients, treatment often leads to chemoresistance. Accumulating evidence has demosntrated that microRNA (miRNA/miR) is involved in drug resistance of glioma cells. Nevertheless, the role of miR‑501‑3p in glioma cell resistance to cisplatin is unclear. In the present study, it was revealed that miR‑501‑3p expression was decreased in glioma tissues and further underexpressed in cisplatin‑resistant glioma cells compared with wild‑type (WT) glioma cells. Furthermore, cisplatin treatment inhibited the level of miR‑501‑3p in a time‑dependent way. Ectopic expression of miR‑501‑3p suppressed glioma cell growth and invasion, but increased cisplatin‑resistant glioma cell apoptosis. Furthermore, miR‑501‑3p sensitized glioma cells to cisplatin‑induced proliferation arrest and death. Mechanistically, it was demonstrated that miR‑501‑3p targeted MYCN in glioma cells. In addition, it was revealed that miR‑501‑3p inhibited MYCN expression by a luciferase reporter assay and reverse transcription‑quantitative polymerase chain reaction. Notably, restoration of MYCN reversed the effects of miR‑501‑3p in cisplatin‑resistant glioma cells. In conclusion, these results suggested that miR‑501‑3p may serve a promising marker for cisplatin resistance.
顺铂是一种常用于治疗脑胶质瘤患者的化疗药物,但治疗往往会导致化疗耐药。越来越多的证据表明 microRNA(miRNA/miR)参与了脑胶质瘤细胞的耐药性。然而,miR-501-3p 在脑胶质瘤细胞对顺铂耐药性中的作用尚不清楚。在本研究中,研究人员发现 miR-501-3p 在脑胶质瘤组织中表达下调,并且在顺铂耐药性脑胶质瘤细胞中进一步低表达,而在野生型(WT)脑胶质瘤细胞中则表达较高。此外,顺铂处理以时间依赖性方式抑制 miR-501-3p 的水平。外源性表达 miR-501-3p 抑制脑胶质瘤细胞的生长和侵袭,但增加了顺铂耐药性脑胶质瘤细胞的凋亡。此外,miR-501-3p 使脑胶质瘤细胞对顺铂诱导的增殖抑制和死亡敏感。在机制上,研究人员证明 miR-501-3p 靶向脑胶质瘤细胞中的 MYCN。此外,通过荧光素酶报告基因检测和逆转录-定量聚合酶链反应显示,miR-501-3p 通过抑制 MYCN 表达来发挥作用。值得注意的是,MYCN 的恢复逆转了 miR-501-3p 在顺铂耐药性脑胶质瘤细胞中的作用。综上所述,这些结果表明 miR-501-3p 可能作为顺铂耐药性的有前途的标志物。