Landscape of N-Methyladenosine Modification Patterns in Human Ameloblastoma.

OBJECTIVE

To comprehensively analyze the global N-methyladenosine (mA) modification pattern in ameloblastoma.

METHODS

mA peaks in ameloblastoma and normal oral tissues were detected by MeRIP-seq. Differentially methylated mA sites within messenger RNAs (mRNAs), long no-coding RNA (lncRNAs) and circular RNA (circRNAs) were identified, followed by functional enrichment analysis. By comprehensively analyzing MeRIP-seq and RNA-seq data, differentially expressed mRNAs, lncRNAs and circRNAs containing differentially methylated sites were identified. RNA binding proteins (RBPs) were then identified for differentially methylated mA sites.

RESULTS

In total, 3,673 differentially methylated mA sites within coding genes were detected, of which 16.2% (704/3,673) were significantly upmethylated sites in ameloblastoma compared to normal oral tissues. Furthermore, 4,975 differentially methylated mA sites within lncRNAs were identified, of which 29.4% (1,465/4,975) were upmethylated sites in ameloblastoma. We also found 364 differentially methylated mA sites within circRNAs, of which 22.5% (82/364) were upmethylated sites in ameloblastoma. Differentially methylated mA was most often harbored in the CDS (54.10%), followed by 5'UTR (21.71%). Functional enrichment analysis revealed that mA modification could be involved in the development of ameloblastoma by organism developmental processes. A total of 158 RBPs within differentially methylated mA sites were identified, which were significantly involved in mRNA metabolic process, mRNA processing, RNA processing, RNA splicing and RNA transport.

CONCLUSION

Our findings for the first time provide mA landscape of human ameloblastoma, which expand the understanding of mA modifications and uncover regulation of lncRNAs and circRNAs through mA modification in ameloblastoma.