Department of Neurosurgery, Weifang Yidu Central Hospital, Weifang, Shandong, China (mainland).
Department of Radiotherapy, Weifang Yidu Central Hospital, Weifang, Shandong, China (mainland).
Med Sci Monit. 2018 Sep 20;24:6630-6637. doi: 10.12659/MSM.910292.
BACKGROUND The aim of this study was to assess the utility of miR-126 in promoting malignant glioma progression and determine if miR-126 might be a target for malignant glioma treatment. MATERIAL AND METHODS The expression of miR-126 in malignant glioma tissues and cells was detected by reverse transcription polymerase chain reaction (RT-PCR). Western blot analysis was used to detect changes in protein levels. Transwell assay was applied to assess the migration and invasion in vitro. Luciferase reporter assay was used to confirm the binding of miR-126 and mature T cell proliferation 1 (MTCP1). A nude mouse tumor model was used to assess the molecular mechanism in vivo. RESULTS The expression level of miR-126 in patients with stage IIIIV malignant glioma was significant lower than that in patients with stage III. In different malignant glioma cell lines, the expression was significantly reduced in U87MG. Compared with the control mimics group, the expression of MTCP1 was significantly decreased. The results of Transwell assay showed that the invasiveness and migration in the miR-126 mimics group was significantly lower than in the control mimics groups. miR-126 mimics did not affect luciferase activity in the Mut-miR-126/MTCP1 group, while miR-126 mimics reduced luciferase activity by 54% in the Wt-miR-126/MTCP1 group. The results of invasion showed that the invasion ability in the miR-126 inhibitor group was significantly increased compared with that in the normal control (NC) group, while the invasion and migration abilities in the MTCP1 siRNA group were significantly increased. After 6 weeks, the tumor volume in the miR-126 inhibitor group was significantly increased, while that in the MTCP1 siRNA group was significantly decreased. CONCLUSIONS miR-126 inhibits the migration of malignant glioma cells by inhibiting MTCP1.
本研究旨在评估 miR-126 在促进恶性神经胶质瘤进展中的作用,并确定 miR-126 是否可能成为恶性神经胶质瘤治疗的靶点。
采用逆转录聚合酶链反应(RT-PCR)检测恶性神经胶质瘤组织和细胞中 miR-126 的表达。采用 Western blot 分析检测蛋白水平的变化。采用 Transwell 实验评估体外迁移和侵袭。应用荧光素酶报告实验证实 miR-126 与成熟 T 细胞增殖 1(MTCP1)的结合。采用裸鼠肿瘤模型体内评估分子机制。
IIIIV 期恶性神经胶质瘤患者 miR-126 表达水平显著低于 III 期患者。在不同的恶性神经胶质瘤细胞系中,U87MG 细胞系中表达显著降低。与对照 mimics 组相比,MTCP1 的表达明显降低。Transwell 实验结果显示,miR-126 mimics 组的侵袭和迁移能力明显低于对照 mimics 组。miR-126 mimics 对 Mut-miR-126/MTCP1 组的荧光素酶活性没有影响,而 miR-126 mimics 使 Wt-miR-126/MTCP1 组的荧光素酶活性降低了 54%。侵袭实验结果表明,miR-126 抑制剂组的侵袭能力明显高于正常对照组(NC 组),而 MTCP1 siRNA 组的侵袭和迁移能力明显增强。6 周后,miR-126 抑制剂组的肿瘤体积明显增大,而 MTCP1 siRNA 组的肿瘤体积明显减小。
miR-126 通过抑制 MTCP1 抑制恶性神经胶质瘤细胞的迁移。