Department of Neurosurgery, The Second Affiliated Hospital of Nanchang University, Nanchang, Jiangxi Province 330006, China.
East China Institute of Digital Medical Engineering, Shangrao, Jiangxi Province 334000, China.
Comput Math Methods Med. 2021 Oct 26;2021:7566365. doi: 10.1155/2021/7566365. eCollection 2021.
Numerous lncRNAs were found as regulatory factors for occurrence and progression of various tumors, but there is still less research on the role of lncRNAs in malignant progression of glioma.
Bioinformatics analysis analyzed differential genes (DEGs) in the TCGA database. MTT, flow cytometry, and Transwell assays were performed to test the proliferation, apoptosis, migration, and invasion of cells. qRT-PCR and western blot were conducted to detect RNA and protein expressions of each gene, respectively. CHIP assay verified the binding relationship between genes. FISH assayed subcellar location of CRNDE, and xenograft in nude mice was performed for verification.
CRNDE was upregulated in glioma cells, and overexpression of CRNDE facilitated malignant progression of glioma cells. CRNDE regulated occurrence and development of glioma through the CRNDE-ETS1-GPR17 axis. ETS1 was proved to target promoter region of GPR17. Overexpression of CRNDE promoted the binding between ETS1 and the promoter region of GPR17, thus, promoting the transcription of GPR17, while silencing of GPR17 inhibited promotion of CRNDE on proliferation, migration, and invasion of glioma cells.
These results demonstrated that CRNDE regulated GPR17 expression by binding ETS1, a transcription factor, thereby affecting glioma development. The results also indicated that CRNDE could serve as a possible therapeutic target and prognostic biomarker for glioma.
大量长链非编码 RNA（lncRNA）被发现作为各种肿瘤发生和发展的调节因子，但关于 lncRNA 在胶质瘤恶性进展中的作用研究仍较少。
通过生物信息学分析 TCGA 数据库中的差异基因（DEGs）。采用 MTT、流式细胞术和 Transwell 实验检测细胞的增殖、凋亡、迁移和侵袭能力。通过 qRT-PCR 和 Western blot 分别检测各基因的 RNA 和蛋白表达水平。CHIP 实验验证基因之间的结合关系。FISH 检测 CRNDE 的亚细胞定位，裸鼠异种移植实验进行验证。
CRNDE 在胶质瘤细胞中呈上调表达，过表达 CRNDE 促进了胶质瘤细胞的恶性进展。CRNDE 通过 CRNDE-ETS1-GPR17 轴调控胶质瘤的发生发展。ETS1 被证明靶向 GPR17 的启动子区域。CRNDE 的过表达促进了 ETS1 与 GPR17 启动子区域的结合，从而促进 GPR17 的转录，而 GPR17 的沉默抑制了 CRNDE 对胶质瘤细胞增殖、迁移和侵袭的促进作用。
这些结果表明，CRNDE 通过结合转录因子 ETS1 调节 GPR17 的表达，从而影响胶质瘤的发展。研究结果还表明，CRNDE 可作为胶质瘤的潜在治疗靶点和预后生物标志物。
