Landscape of N(6)-Methyladenosine Modification Patterns in Human Ameloblastoma

OBJECTIVE: To comprehensively analyze the global N(6)-methyladenosine (m(6)A) modification pattern in ameloblastoma. METHODS: m(6)A peaks in ameloblastoma and normal oral tissues were detected by MeRIP-seq. Differentially methylated m(6)A 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 m(6)A sites. RESULTS: In total, 3,673 differentially methylated m(6)A 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 m(6)A sites within lncRNAs were identified, of which 29.4% (1,465/4,975) were upmethylated sites in ameloblastoma. We also found 364 differentially methylated m(6)A sites within circRNAs, of which 22.5% (82/364) were upmethylated sites in ameloblastoma. Differentially methylated m(6)A was most often harbored in the CDS (54.10%), followed by 5’UTR (21.71%). Functional enrichment analysis revealed that m(6)A modification could be involved in the development of ameloblastoma by organism developmental processes. A total of 158 RBPs within differentially methylated m(6)A 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 m(6)A landscape of human ameloblastoma, which expand the understanding of m(6)A modifications and uncover regulation of lncRNAs and circRNAs through m(6)A modification in ameloblastoma.