Abstract
BackgroundInvasive malignant pleomorphic adenoma (IMPA) is a highly invasive parotid gland tumor and lacks effective therapy. N6-Methyladenosine (m6A) 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 m6A-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 m6A methylation in mRNA.MethodsMethylated RNA immunoprecipitation with next-generation sequencing (MeRIP-seq) and RNA sequencing (RNA-seq) were utilized to acquire the first transcriptome-wide profiling of the m6A methylome map in IMPA followed by bioinformatics analysis.ResultsIn this study, we obtained m6A methylation maps of IMPA samples and normal adjacent tissues through MeRIP-seq. In total, 25,490 m6A peaks associated with 13,735 genes were detected in the IMPA group, whereas 33,930 m6A 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 m6A-containing genes were significantly enriched in cancer and metabolism relevant pathways. Furthermore, we identified a relationship between the m6A methylome and the RNA transcriptome, indicating a mechanism by which m6A modulates gene expression.ConclusionsOur study is the first to provide comprehensive and transcriptome-wide profiles to determine the potential roles played by m6A methylation in IMPA. These results may open new avenues for in-depth research elucidating the m6A topology of IMPA and the molecular mechanisms governing the formation and progression of IMPA.
Highlights
Pleomorphic adenoma (PA), one of the most common types of salivary neoplasms, typically occurs in the superficial lobe of the parotid gland and accounts for 60–70% of all parotid tumors [1]
25,490 m6A peaks associated with 13,735 genes were detected in the Invasive malignant pleomorphic adenoma (IMPA) group, whereas 33,930 m6A peaks associated with 18,063 genes were detected in the control group
Our study is the first to provide comprehensive and transcriptome-wide profiles to determine the potential roles played by m6A methylation in IMPA
Summary
Pleomorphic adenoma (PA), one of the most common types of salivary neoplasms, typically occurs in the superficial lobe of the parotid gland and accounts for 60–70% of all parotid tumors [1]. MPA can be further classified into three subtypes according to the depth of tumor infiltration beyond the capsule of the previous PA, namely, Han et al Cancer Cell Int (2021) 21:142 non-invasive, micro-invasive, and invasive malignant pleomorphic adenoma (IMPA) [4]. Traditional molecular-targeted drugs against estrogen receptors (ER) or human epidermal growth factor receptor 2 (HER2) are of limited efficiency in treating IMPA, since a variety of patients are negative for both ER and HER2. To circumvent these obstacles, further research is necessary to identify a new molecular basis of IMPA. Invasive malignant pleomorphic adenoma (IMPA) is a highly invasive parotid gland tumor and lacks effective therapy. In this study, we attempted to profile the effect of IMPA in terms of m6A methylation in mRNA
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