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微小RNA-155通过PI3K/AKT信号通路调控胶质瘤细胞的增殖

miR-155 Regulates the Proliferation of Glioma Cells Through PI3K/AKT Signaling.

作者信息

Wu Dahao, Wang Changzhen

机构信息

Department of Neurosurgery, Shandong Provincial ENT Hospital, Shandong Provincial ENT Hospital Affiliated to Shandong University, Jinan, China.

出版信息

Front Neurol. 2020 Apr 28;11:297. doi: 10.3389/fneur.2020.00297. eCollection 2020.

Abstract

Micro-RNA plays a critical role in the pathological process of gliomas. Previous research showed that the level of miR-155 was significantly increased in many cancers, including gliomas. However, the mechanism of glioma is still unknown. To investigate the regulatory function of miR-155 on glioma U87-MG cells and its effects on related signaling pathways. After transfection of miR-155 mimic and inhibitor, the level of miR-155 were applied to detect cell proliferation, apoptosis, senescence index, invasive ability and cell migration at different time points (0, 24, 24 h, respectively) by CCK8 assay, flow cytometry, β-galactosidase (β-gal) staining, transwell and scratch test, respectively. The effect of miR-155 on PI3K/AKT signal pathway was observed at meantime. Compared with the control group, after miR-155 mimic transfection, U87-MG cell viability, cell migration rate and invasiveness were increased, while apoptosis and senescence were significantly decreased, which was the opposite on miR-155 inhibitor transfection. The phosphorylation levels of miR-155, PI3K, AKT, PI3K, and AKT in U87-MG cells intervened with miR-155 mimic also increased significantly, while the levels of PTEN, Caspase-3, Caspase-9 mRNA, and protein declined significantly, with statistically significant difference. Meanwhile, compared with the control group, miR-155 inhibitor group were on the contrary. The study indicated that miR-155 take charge a key function in regulating the proliferation, migration, and invasion of glioma U87-MG cells through PI3K/AKT signaling pathway, and has anti-glioma effects by inhibition of miR-155, which provided ideas for further clinical treatment of glioma patients.

摘要

微小RNA在胶质瘤的病理过程中起关键作用。先前的研究表明,miR-155水平在包括胶质瘤在内的多种癌症中显著升高。然而,胶质瘤的发病机制仍不清楚。为了研究miR-155对胶质瘤U87-MG细胞的调控作用及其对相关信号通路的影响。转染miR-155模拟物和抑制剂后,分别通过CCK8法、流式细胞术、β-半乳糖苷酶(β-gal)染色、Transwell实验和划痕实验,在不同时间点(分别为0、24、48小时)检测miR-155水平,以检测细胞增殖、凋亡、衰老指数、侵袭能力和细胞迁移。同时观察miR-155对PI3K/AKT信号通路的影响。与对照组相比,转染miR-155模拟物后,U87-MG细胞活力、细胞迁移率和侵袭性增加,而凋亡和衰老显著降低,miR-155抑制剂转染后则相反。用miR-155模拟物干预的U87-MG细胞中,miR-155、PI3K、AKT的磷酸化水平也显著增加,而PTEN、Caspase-3、Caspase-9 mRNA和蛋白水平显著下降,差异有统计学意义。同时,与对照组相比,miR-155抑制剂组则相反。研究表明,miR-155通过PI3K/AKT信号通路在调节胶质瘤U87-MG细胞的增殖、迁移和侵袭中起关键作用,抑制miR-155具有抗胶质瘤作用,为胶质瘤患者的进一步临床治疗提供了思路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d47/7198892/3f20fdc0f275/fneur-11-00297-g0001.jpg

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