Journal
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
Volume 25, Issue 15, Pages 7204-7217Publisher
WILEY
DOI: 10.1111/jcmm.16750
Keywords
CircRNA; decoration pattern; GBM; glioblastoma; N6-methyladenosine modification; ncRNA; noncoding RNA
Categories
Funding
- Government-funded Clinical Medicine Outstanding Talent Training Project(Team) [360017]
- Natural Science Foundations of Hebei Province [H2020201050, H2020201206]
- Graduate Innovative Ability Training Projects of Hebei University [hbu2020bs003]
- Graduate Innovative Ability Training Projects of Hebei University of Chinese Medicine [XCXZZBS2020002]
- Outstanding Student Scientific Research Ability Improvement Projects of Hebei University of Chinese Medicine [YXZ2019002]
- Science and Technology Capacity Improvement Projects of Hebei University of Chinese Medicine [KTZ2019019]
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This study systematically characterized the N6-methyladenosine modification pattern of circular RNAs in glioblastoma, identifying potential roles of N6-methyladenosine-modified circRNAs in the development of GBM. Through comprehensive RNA methylation sequencing and bioinformatics analysis, key molecules associated with N6-methyladenosine-mediated GBM progression were identified for further investigation.
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.
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