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Identification and characterization of N6-methyladenosine modification of circRNAs in glioblastoma |
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| Authors: | Yuhao Zhang Xiuchao Geng Jianglong Xu Qiang Li Liangchao Hao Zhaomu Zeng Menglin Xiao Jia Song Fulin Liu Chuan Fang Hong Wang |
| Institution: | 1. Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China
School of Clinical Medicine, Hebei University, Baoding, China Contribution: Conceptualization (equal), Writing - original draft (equal);2. School of Medicine, Taizhou University, Taizhou, China Faculty of Integrated Traditional Chinese and Western Medicine, Hebei University of Chinese Medicine, Shijiazhuang, China Contribution: Conceptualization (equal), Writing - original draft (equal);3. Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China Contribution: Writing - original draft (equal);4. Faculty of Acupuncture-Moxibustion and Tuina, Hebei University of Chinese Medicine, Shijiazhuang, China Contribution: Methodology (equal);5. Department of Plastic Surgery, Shaoxing People's Hospital, Shaoxing, China Contribution: Methodology (equal);6. Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China School of Clinical Medicine, Hebei University, Baoding, China Contribution: ?Investigation (supporting), Software (supporting), Validation (supporting);7. School of Basic Medicine, Hebei University, Baoding, China Contribution: ?Investigation (supporting), Validation (supporting);8. Office of Academic Research, Affiliated Hospital of Hebei University, Baoding, China;9. Department of Neurosurgery, Affiliated Hospital of Hebei University, Baoding, China |
| Abstract: | 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. |
| Keywords: | CircRNA decoration pattern GBM glioblastoma N6-methyladenosine modification ncRNA noncoding RNA |