Sun Shupeng, Wang Xiuyu, Xu Xinnv, Di Hui, Du Jixiang, Xu Bin, Wang Qiong, Wang Jinhuan
Tianjin Key Laboratory of Cerebral Vascular and Neurodegenerative Diseases, Tianjin Neurosurgical Institute, Department of Neurosurgery, Tianjin Huanhu Hospital, Tianjin 300350, China.
The Graduate School, Tianjin Medical University, Tianjin 300070, China.
Oncotarget. 2017 Jan 17;8(3):5057-5068. doi: 10.18632/oncotarget.13789.
Previous studies reported that miR-433 exerts function widely in human tumorigenesis and development. Here, we further investigate the potential role of miR-433 in glioma. Quantitative real-time PCR demonstrated that miR-433-3p and miR-433-5p were low expressed in glioma tissues and cell lines. Functional studies suggested that the overexpression of miR-433-3p suppressed proliferation, induced apoptosis and inhibited invasion and migration of human glioma cells. But the growth and metastasis of glioma cells were not significantly influenced by overexpression of miR-433-5p. In a xenograft model, we also showed that miR-433-3p had an inhibitory effect on the growth of glioma. Bioinformatics coupled with luciferase and western blot assays revealed that CREB is a direct target of miR-433-3p, and the overexpression of CREB can rescue the phenotype changes induced by miR-433-3p overexpression. Besides, miR-433-3p could increase chemosensitivity of glioma to temozolomide by targeting CREB in vitro and in vivo. Taken together, these results suggest that miR-433-3p may function as a potential marker in diagnostic and therapeutic target for glioma.
先前的研究报道,miR-433在人类肿瘤发生和发展过程中发挥着广泛的作用。在此,我们进一步研究miR-433在胶质瘤中的潜在作用。定量实时PCR结果显示,miR-433-3p和miR-433-5p在胶质瘤组织和细胞系中低表达。功能研究表明,miR-433-3p的过表达抑制了人胶质瘤细胞的增殖,诱导了细胞凋亡,并抑制了其侵袭和迁移。但miR-433-5p的过表达对胶质瘤细胞的生长和转移没有显著影响。在异种移植模型中,我们还发现miR-433-3p对胶质瘤的生长具有抑制作用。生物信息学分析结合荧光素酶和蛋白质免疫印迹分析显示,CREB是miR-433-3p的直接靶点,CREB的过表达可挽救miR-433-3p过表达诱导的表型变化。此外,miR-433-3p在体外和体内均可通过靶向CREB增加胶质瘤对替莫唑胺的化疗敏感性。综上所述,这些结果表明miR-433-3p可能作为胶质瘤诊断和治疗靶点的潜在标志物。