Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China; Department of Neurosurgery, Sichuan Academy of Medical Sciences and Sichuan Provincial People's Hospital, School of Medicine, University of Electronic Science and Technology of China, Chengdu 610072, Sichuan, China.
Department of Neurosurgery, West China Hospital of Sichuan University, Chengdu 610041, Sichuan, China.
Biochem Biophys Res Commun. 2018 Jun 7;500(3):569-576. doi: 10.1016/j.bbrc.2018.04.091. Epub 2018 Apr 25.
Glioblastoma (GB) is the most common and deadliest malignant primary brain tumor with a high recurrence. In this study, lncRNA UCA1/miR-182 axis has been regarded as a nodal driver of glioma invasion mediated by GB-associated stromal cells (GASCs) and GASC-secreted chemokine CXCL14. In clinical specimens, CXCL14 upregulation in GASCs also correlated with poor prognosis. Notably, CXCL14-high GASCs mediated lncRNA UCA1 upregulation and miR-182 downregulation in glioma cells. Moreover, miR-182 directly bound to the fructose-2,6-biphosphatase PFKFB2; UCA1/miR-182 axis thereby modulated GASC-induced glycolysis in glioma cells. Overall, UCA1/miR-182/PFKFB2 axis modulates chemokine CXCL14 secretion, glycolysis and invasion of glioma cells in GASCs.
胶质母细胞瘤(GB)是最常见和最致命的恶性原发性脑肿瘤,具有高复发率。在这项研究中,lncRNA UCA1/miR-182 轴被认为是由胶质母细胞瘤相关基质细胞(GASCs)和 GASC 分泌的趋化因子 CXCL14 介导的神经胶质瘤侵袭的关键驱动因素。在临床标本中,GASCs 中 CXCL14 的上调也与预后不良相关。值得注意的是,CXCL14 高表达的 GASCs 介导了胶质瘤细胞中 lncRNA UCA1 的上调和 miR-182 的下调。此外,miR-182 直接结合果糖-2,6-二磷酸酶 PFKFB2;UCA1/miR-182 轴从而调节 GASC 诱导的胶质瘤细胞中的糖酵解。总的来说,UCA1/miR-182/PFKFB2 轴调节趋化因子 CXCL14 的分泌、糖酵解和 GASCs 中胶质瘤细胞的侵袭。