Liu Liang, Li Xiaojian, Wu Heming, Tang Yong, Li Xiang, Shi Yan
Department of Neurosurgery, Nanjing First Hospital, Nanjing Medical University, Nanjing, China.
Front Oncol. 2021 Jul 26;11:648152. doi: 10.3389/fonc.2021.648152. eCollection 2021.
Glioma is the most common primary tumour of the central nervous system and is considered one of the greatest challenges for neurosurgery. Mounting evidence has shown that lncRNAs participate in various biological processes of tumours, including glioma. This study aimed to reveal the role and relevant mechanism of COX10-AS1 in glioma. The expression of COX10-AS1, miR-641 and E2F6 was measured by qRT-PCR and/or western blot. Clone formation assays, EdU assays, Transwell assays and tumour xenograft experiments were performed to evaluate the effects of COX10-AS1, miR-641 and E2F6 on glioma proliferation, migration and invasion. Luciferase reporter assays, RNA pull-down assays and ChIP assays were conducted to analyse the relationship among COX10-AS1, miR-641 and E2F6. We demonstrated that COX10-AS1 was upregulated in glioma tissues and cell lines, which was related to the grade of glioma and patient survival. Next, through functional assays, we found that COX10-AS1 influenced the proliferation, migration and invasion of glioma cell lines. Then, with the help of bioinformatics analysis, we confirmed that COX10-AS1 regulated glioma progress by acting as a sponge of miR-641 to regulate E2F6. Moreover, further study indicated that E2F6 could promote COX10-AS1 expression by binding to its promoter region. Taken together, the data indicated that COX10-AS1 acts as an oncogene in combination with COX10-AS1/miR-641/E2F6 in glioma, which may be beneficial to the diagnosis and treatment of glioma.
胶质瘤是中枢神经系统最常见的原发性肿瘤,被认为是神经外科面临的最大挑战之一。越来越多的证据表明,长链非编码RNA(lncRNAs)参与肿瘤的各种生物学过程,包括胶质瘤。本研究旨在揭示COX10-AS1在胶质瘤中的作用及相关机制。通过qRT-PCR和/或蛋白质免疫印迹法检测COX10-AS1、miR-641和E2F6的表达。进行克隆形成实验、EdU实验、Transwell实验和肿瘤异种移植实验,以评估COX10-AS1、miR-641和E2F6对胶质瘤增殖、迁移和侵袭的影响。进行荧光素酶报告基因实验、RNA下拉实验和染色质免疫沉淀实验,以分析COX10-AS1、miR-641和E2F6之间的关系。我们证明COX10-AS1在胶质瘤组织和细胞系中上调,这与胶质瘤的分级和患者生存有关。接下来,通过功能实验,我们发现COX10-AS1影响胶质瘤细胞系的增殖、迁移和侵袭。然后,借助生物信息学分析,我们证实COX10-AS1通过充当miR-641的海绵来调节E2F6,从而调控胶质瘤进展。此外,进一步研究表明,E2F6可通过结合其启动子区域促进COX10-AS1表达。综上所述,数据表明COX10-AS1在胶质瘤中与COX10-AS1/miR-641/E2F6结合发挥癌基因作用,这可能有助于胶质瘤的诊断和治疗。