Chen Xiang-Rui, Zhang Yan-Guo, Wang Qiang
Department of Neurosurgery, The Third Affiliated Hospital of Qiqihar Medical Unversity, Qiqihar, China.
Front Oncol. 2021 Aug 31;11:661653. doi: 10.3389/fonc.2021.661653. eCollection 2021.
Chemotherapy combined with surgery is an important clinical treatment for glioma, but endogenous or acquired temozolomide (TMZ) resistance can lead to poor prognosis. microRNA (miR)-9-5p acts in biological function of glioma, but the drug resistance of miR-9-5p in glioma is under exploration. The study intended to test the molecular mechanism of miR-9-5p in glioma cells. MTT assay was applied to investigate the chemosensitivity enhancement of miR-9-5p on TMZ in glioma cells U87-TMZ and U251-TMZ, and experiments confirmed its role on tumor growth in nude mice. The results of double luciferase reporter gene assay, qRT-PCR and WB indicated that miR-9-5p directly targeted ABCC1 (ATP binding cassette subfamily C member 1) to reduce its expressions. MTT and flow cytometry indicated that elevation of miR-9-5p or down-regulation of ABCC1 could inhibit proliferation-induced apoptosis of drug-resistant cells, and the decrease of miR-9-5p could reverse the reduction of ABCC1 on proliferation-induced apoptosis of drug-resistant cells. In vivo experiments showed that miR-9-5p could promote the anti-tumor role of TMZ. To sum up, the increase of miR-9-5p directly targets ABCC1 and may make glioma cells sensitive to TMZ.
化疗联合手术是胶质瘤重要的临床治疗手段,但内源性或获得性替莫唑胺(TMZ)耐药可导致预后不良。微小RNA(miR)-9-5p在胶质瘤生物学功能中发挥作用,但其在胶质瘤中的耐药性尚在探索中。本研究旨在检测miR-9-5p在胶质瘤细胞中的分子机制。采用MTT法研究miR-9-5p对胶质瘤细胞U87-TMZ和U251-TMZ中TMZ的化疗敏感性增强作用,并通过实验证实其对裸鼠肿瘤生长的作用。双荧光素酶报告基因检测、qRT-PCR和WB结果表明,miR-9-5p直接靶向ABCC1(ATP结合盒亚家族C成员1)以降低其表达。MTT和流式细胞术表明,miR-9-5p升高或ABCC1下调可抑制耐药细胞增殖诱导的凋亡,而miR-9-5p降低可逆转ABCC1对耐药细胞增殖诱导凋亡的抑制作用。体内实验表明,miR-9-5p可促进TMZ的抗肿瘤作用。综上所述,miR-9-5p增加直接靶向ABCC1,可能使胶质瘤细胞对TMZ敏感。