Comprehensive analysis of the transcriptome-wide m6A methylome in invasive malignant pleomorphic adenoma

Background: Invasive malignant pleomorphic adenoma (IMPA) is a highly invasive parotid gland tumor and lacks effective therapy. N6-Methyladenosine (m(6)A) is the most prevalent post-transcriptional modification of mRNAs in eukaryotes and plays an important role in the pathogenesis of multiple tumors. However, the significance of m(6)A-modified mRNAs in IMPA has not been elucidated to date. Hence, in this study, we attempted to profile the effect of IMPA in terms of m(6)A methylation in mRNA. Methods: Methylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were utilized to acquire the first transcriptome-wide profiling of the m(6)A methylome map in IMPA followed by bioinformatics analysis. Results: In this study, we obtained m(6)A methylation maps of IMPA samples and normal adjacent tissues through MeRIP-seq. In total, 25,490 m(6)A peaks associated with 13,735 genes were detected in the IMPA group, whereas 33,930 m(6)A peaks associated with 18,063 genes were detected in the control group. Peaks were primarily enriched within coding regions and near stop codons with AAACC and GGAC motifs. Moreover, functional enrichment analysis demonstrated that m(6)A-containing genes were significantly enriched in cancer and metabolism relevant pathways. Furthermore, we identified a relationship between the m(6)A methylome and the RNA transcriptome, indicating a mechanism by which m(6)A modulates gene expression. Conclusions: Our study is the first to provide comprehensive and transcriptome-wide profiles to determine the potential roles played by m(6)A methylation in IMPA. These results may open new avenues for in-depth research elucidating the m(6)A topology of IMPA and the molecular mechanisms governing the formation and progression of IMPA.