Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China.
School of Clinical Medicine, Hebei University, Baoding, China.
J Cell Mol Med. 2021 Aug;25(15):7204-7217. doi: 10.1111/jcmm.16750. Epub 2021 Jun 27.
This research systematically profiled the global N6-methyladenosine modification pattern of circular RNAs (circRNAs) in glioblastoma (GBM). Based on RNA methylation sequencing (MeRIP sequencing or N6-methyladenosine sequencing) and RNA sequencing, we described the N6-methyladenosine modification status and gene expression of circRNAs in GBM and normal brain tissues. N6-methyladenosine-related circRNAs were immunoprecipitated and validated by real-time quantitative PCR. Bioinformatics analysis and related screening were carried out. Compared with those of the NC group, the circRNAs from GBM exhibited 1370 new N6-methyladenosine peaks and 1322 missing N6-methyladenosine peaks. Among the loci associated with altered N6-methyladenosine peaks, 1298 were up-regulated and 1905 were down-regulated. The N6-methyladenosine level tended to be positively correlated with circRNA expression. Bioinformatics analysis was used to predict the biological function of N6-methyladenosine-modified circRNAs and the corresponding signalling pathways. In addition, through PCR validation combined with clinical data mining, we identified five molecules of interest (BUB1, C1S, DTHD1, F13A1 and NDC80) that could be initial candidates for further study of the function and mechanism of N6-methyladenosine-mediated GBM development. In conclusion, our findings demonstrated the N6-methyladenosine modification pattern of circRNAs in human GBM, revealing the possible roles of N6-methyladenosine-mediated novel noncoding RNAs in the origin and progression of GBM.
本研究系统地描绘了神经胶质瘤（GBM）中环状 RNA（circRNA）的全球 N6-甲基腺苷修饰模式。基于 RNA 甲基化测序（MeRIP 测序或 N6-甲基腺苷测序）和 RNA 测序，我们描述了 GBM 和正常脑组织中 circRNA 的 N6-甲基腺苷修饰状态和基因表达。通过实时定量 PCR 对 N6-甲基腺苷相关 circRNA 进行免疫沉淀和验证。进行了生物信息学分析和相关筛选。与 NC 组相比，GBM 的 circRNAs 表现出 1370 个新的 N6-甲基腺苷峰和 1322 个缺失的 N6-甲基腺苷峰。在与改变的 N6-甲基腺苷峰相关的基因座中，有 1298 个上调，1905 个下调。N6-甲基腺苷水平与 circRNA 表达呈正相关。生物信息学分析用于预测 N6-甲基腺苷修饰的 circRNA 的生物学功能和相应的信号通路。此外，通过结合临床数据挖掘的 PCR 验证，我们鉴定了五个有意义的分子（BUB1、C1S、DTHD1、F13A1 和 NDC80），它们可能是进一步研究 N6-甲基腺苷介导的 GBM 发展的功能和机制的初始候选者。总之，我们的研究结果表明了人 GBM 中 circRNA 的 N6-甲基腺苷修饰模式，揭示了 N6-甲基腺苷介导的新型非编码 RNA 在 GBM 的起源和进展中的可能作用。
