Department of Neurosurgery, Liaocheng People's Hospital, Shandong, P.R. China.
Department of Pharmacy, Liaocheng People's Hospital, Shandong, P.R. China.
Oncol Res. 2018 Sep 14;26(8):1143-1154. doi: 10.3727/096504017X14965095236521. Epub 2017 Jun 9.
Gliomas are the most common primary brain tumors with high mortality. The treatment for gliomas is largely limited due to its uncomprehending pathological mechanism. Here we aimed to investigate the effect of long noncoding RNA (lncRNA) coiled-coil domain-containing 26 (CCDC26) in glioma progression. In our study, the expression of CCDC26 was found upregulated in glioma tissues and cell lines compared with normal tissues and cell lines. Further exploration detected decreased cell proliferation and increased cell apoptosis in U-251 and M059J cells transfected with CCDC26-siRNA. In addition, the silencing of CCDC26 strongly reduced the wound closing rate and the number of invasive cells compared with the scramble group. Simultaneously, the expression of miR-203 was found suppressed in glioma tissues and cells lines. Suppressed level of miR-203 was then elevated in U-251 and M059J cells transfected with CCDC26-siRNA. The result of the luciferase activity assay also showed that the luciferase activity was strongly strengthened by adding the miR-203 inhibitor into the CCDC26 WT group. Moreover, CDCC26-siRNA counteracted the effect of the miR-203 inhibitor in facilitating cell viability and mobility in U-251 cells. The in vivo experiment also revealed that CCDC26-siRNA inhibited glioma growth and metastasis. Taken together, our research indicated a CCDC26/miR-203 pathway in regulating the growth and metastasis of gliomas, providing new viewpoints and promising targets for glioma therapy.
神经胶质瘤是最常见的原发性脑肿瘤,死亡率很高。由于其病理机制尚未完全阐明,神经胶质瘤的治疗方法在很大程度上受到限制。本研究旨在探讨长链非编码 RNA(lncRNA)卷曲螺旋结构域包含蛋白 26(CCDC26)在神经胶质瘤进展中的作用。研究发现,与正常组织和细胞系相比,神经胶质瘤组织和细胞系中 CCDC26 的表达上调。进一步研究发现,与 scramble 组相比,转染 CCDC26-siRNA 的 U-251 和 M059J 细胞中细胞增殖减少,细胞凋亡增加。此外,与 scramble 组相比,CCDC26 沉默组细胞划痕愈合率和侵袭细胞数明显降低。同时,在神经胶质瘤组织和细胞系中发现 miR-203 的表达受到抑制。在转染 CCDC26-siRNA 的 U-251 和 M059J 细胞中,miR-203 的表达水平得到恢复。荧光素酶活性测定结果也表明,加入 miR-203 抑制剂可显著增强 CCDC26 WT 组的荧光素酶活性。此外,CCDC26-siRNA 可逆转 miR-203 抑制剂在促进 U-251 细胞活力和迁移中的作用。体内实验也表明,CCDC26-siRNA 抑制神经胶质瘤的生长和转移。综上所述,本研究表明 CCDC26/miR-203 通路在调节神经胶质瘤的生长和转移中起重要作用,为神经胶质瘤的治疗提供了新的观点和有前途的靶点。