Department of Biochemistry and Molecular Biology, Medical School of Southeast University, # 87 Dingjiaqiao, Nanjing, 210009, China.
Key Laboratory for Developmental Genes and Human Disease, Ministry of Education, Institute of Life Sciences, Southeast University, Nanjing, 210096, China.
Mol Neurobiol. 2021 Jul;58(7):3362-3373. doi: 10.1007/s12035-021-02337-6. Epub 2021 Mar 10.
Glioma is the most common type of solid tumour affecting the central nervous system, and the survival rate of patients with glioma is low. However, the mechanism associated with glioma progression remains unclear. Growing evidence suggests that lncRNAs play essential roles in the initiation and progression of tumours, including gliomas. In the present study, we identified and verified the expression of the novel lncRNA RP11-279C4.1 by analyzing the TANRIC database and performing qRT-PCR assays, the results of which revealed its upregulation in glioma tissues and cell lines. The results of multiple functional experiments demonstrated that RP11-279C4.1 knockdown inhibited glioma malignant phenotypes, including cell proliferation, migration, invasion and cell self-renew ability in vitro. In addition, RP11-279C4.1 downregulation suppressed tumour growth in vivo. Mechanistically, RP11-279C4.1 induced CBX3 activation via competitively sponging miR-1273g-3p, and rescue assay results confirmed the importance of the RP11-279C4.1/miR-1273g-3p/CBX3 axis. Overall, the results of our present study demonstrated that RP11-279C4.1 functions as an oncogene that promotes tumour progression by modulating the miR-1273g-3p/CBX3 axis in glioma, suggesting that RP11-279C4.1 may be a novel therapeutic target for glioma.
神经胶质瘤是最常见的中枢神经系统实体肿瘤,神经胶质瘤患者的生存率较低。然而,与神经胶质瘤进展相关的机制仍不清楚。越来越多的证据表明,lncRNAs 在肿瘤的发生和发展中起着重要作用,包括神经胶质瘤。在本研究中,我们通过分析 TANRIC 数据库和进行 qRT-PCR 检测,鉴定并验证了新型 lncRNA RP11-279C4.1 的表达,结果显示其在神经胶质瘤组织和细胞系中上调。多项功能实验的结果表明,RP11-279C4.1 敲低抑制了体外神经胶质瘤恶性表型,包括细胞增殖、迁移、侵袭和细胞自我更新能力。此外,RP11-279C4.1 的下调抑制了体内肿瘤的生长。机制上,RP11-279C4.1 通过竞争性海绵吸附 miR-1273g-3p 诱导 CBX3 激活,挽救实验结果证实了 RP11-279C4.1/miR-1273g-3p/CBX3 轴的重要性。总之,本研究结果表明,RP11-279C4.1 通过调节 miR-1273g-3p/CBX3 轴在神经胶质瘤中发挥致癌基因的作用,促进肿瘤进展,提示 RP11-279C4.1 可能是神经胶质瘤的一个新的治疗靶点。