Fang Baojun, Li Guoliang, Xu Chongfu, Hui Yuzuo, Li Gang
Department of Neurosurgery, Qilu Hospital of Shandong University Jinan 250012, Shandong Province, China.
Department of Neurosurgery, Liaocheng People's Hospital Liaocheng 252000, Shandong Province, China.
Am J Transl Res. 2018 May 15;10(5):1324-1336. eCollection 2018.
Continuous activation of the Wnt/β-Catenin signaling has been reported to play important roles in multiple process of tumor progression, leading to uncontrolled cancer cell proliferation, growth, and survival. However, the mechanism underlying the regulation of the Wnt/β-Catenin pathway remains largely unknown. Determining the molecular mechanism of the Wnt/β-Catenin pathway's aberrant activation in glioma carcinogenesis might improve therapeutic strategies for patients with glioma. In this study, we showed that the expression of microRNA miR-1249 was markedly upregulated in glioma cell lines and tissues. Upregulation of miR-1249 enhanced, whereas downregulation inhibited, the proliferation of glioma cells both and . Furthermore, bioinformatic and experimental approaches showed that miR-1249 targets and suppresses APC2 expression, an important Wnt/β-Catenin pathway-regulated factor. These data suggested that miR-1249 could be a novel therapeutic target of microRNA-mediated cell proliferation in glioma.
据报道,Wnt/β-连环蛋白信号通路的持续激活在肿瘤进展的多个过程中发挥重要作用,导致癌细胞不受控制地增殖、生长和存活。然而,Wnt/β-连环蛋白通路的调控机制在很大程度上仍然未知。确定Wnt/β-连环蛋白通路在胶质瘤发生过程中异常激活的分子机制可能会改善胶质瘤患者的治疗策略。在本研究中,我们发现微小RNA miR-1249在胶质瘤细胞系和组织中的表达明显上调。miR-1249的上调增强了胶质瘤细胞的增殖,而下调则抑制了其增殖。此外,生物信息学和实验方法表明,miR-1249靶向并抑制APC2的表达,APC2是一种重要的Wnt/β-连环蛋白通路调节因子。这些数据表明,miR-1249可能是胶质瘤中微小RNA介导的细胞增殖的一个新的治疗靶点。