Landscape of N6-Methyladenosine Modification Patterns in Human Ameloblastoma

Abstract

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.

Transcriptome-wide m6A profiling reveals mRNA post-transcriptional modification of boar sperm during cryopreservation

“…Moreover, m 6 A methylation patterns in sperm are the same as in other tissues of the pig, such as fat and muscle [ 66 ], which further confirms that features of RNA m 6 A methylation are conserved in pig. We identified numerous m 6 A peaks that varied widely among individual transcripts, and most of them harbored only one or two m 6 A peaks, which was consistent with previous studies in humans [ 67 ] and chickens [ 68 ]. Analysis at the whole chromosome level showed that mRNAs containing altered m 6 A peaks were transcribed from all chromosomes, especially autosomes [ 67 , 69 ], indicating that m 6 A modification patterns in Fts are widely changed and may involve many pathways that influence the function of sperm.…”

METTL3/YTHDF2 m6A axis accelerates colorectal carcinogenesis through epigenetically suppressing YPEL5

“…In addition, we demonstrated that high expression of METTL3 predicted poor overall survival in CRC, suggesting that METTL3 was a candidate prognostic biomarker for CRC. Cell-free mRNA circulated in plasma or serum samples has been identified to be noninvasive biomarkers for diagnosing and staging multiple cancers [33,34]. Although the concentration of ribonucleases was high in blood, it was practical to detect cell-free mRNA in plasma or serum of CRC patients due to the protection of microvesicles [35,36].…”

“…Although m6A sites preferentially appeared around near stop codons and in 3' UTR, a growing number of studies have demonstrated that m6A methylation in CDS may be more dynamic than those in 3 0 UTR [33]. Niu et al [34] have reported that differentially methylated m6A is most often located in the CDS (54.10%) and followed by 5 0 UTR (21.71%). Mao et al [35] have showed that genes participated in transcriptional regulation are overrepresented among mRNAs with CDS methylation.…”

“…Niu et al . [34] have reported that differentially methylated m6A is most often located in the CDS (54.10%) and followed by 5′UTR (21.71%). Mao et al .…”

N6-Methyladenosine Modification Opens a New Chapter in Circular RNA Biology

“…In human ameloblastoma, Niu et al (2020) investigated the global m6A modification, including in mRNAs, lncRNAs and circRNAs. They found 3,673 differentially methylated m6A sites in mRNAs, 4,975 differentially methylated m6A sites in lncRNAs and 364 differentially methylated m6A sites within circRNAs.…”