Genetics and Epigenetics of RNA Methylation System in Human Cancers

The recently identified RNA modification system has been demonstrated to play important roles in human cancer, immune diseases and mental disorders. The general functions and roles of m6A modification, such as N6-methyladenosine (m6A) and N1-methyladenosine (m1A), have been well described in the past decades, including m6A machines (writer, eraser, and reader genes) and systems, the role of m6A on splicing, RNA exporting, RNA stability, protein translate and specific abnormalities in individual cancers. However, the pan-cancer and cancer-specific m6A variation and characteristics are still unknown. Recent technological advancements such as MeRIP-Seq/m6A-seq have allowed considerable progress in understanding the role played by m6A/m1A RNA modification mechanisms in the pathogenesis of human cancers. Genome-wide RNA methylation studies have been completed in several cancers such as liver cancer and lung cancer. However, genome-wide RNA modification profiles for the majority of cancers are still needed, especially m1A patterns. In addition, the details of the mechanism and the heterogeneity of how m6A/m1A genes regulate mRNA modification to influence cancer development and prognosis are still unknown. Since distinct patterns of DNA and RNA methylation are associated with specific cancer types they show interesting prognostic potential and play an important role in favorable treatment selection, which is important in precision medicine. Finally, recent evidence suggests that RNA-modifying proteins, such as METTL3 and METTL14, can be promising novel targets for cancer treatments.

In this Research Topic, we would like to focus on the mRNA modification system in human cancers. We welcome the submission of Mini-reviews, Reviews and Original Research articles related to genetic (germline and somatic) and epigenetic variations (DNA methylation and histone modifications) in m6A/m1A genes and the consequence to human cancers as well eQTL, meQTL and miRNA/lncRNA regulation of m6A/m1A genes. This Research Topic will cover but not be limited to the following:

1. Genome-wide m6A/m1A landscape research for different human cells or tissues and compared profile differences between different cancers. Identification of m6A/m1A sites of interest which are involved in gene expression regulation, mRNA stability and protein translation efficiency. For such research, we require solid techniques such as MeRIP-Seq/m6A-seq and we welcome all novel m6A/m1A detection biotech assay and computational analysis pipeline to accelerate m6A related research. NGS data must be deposited to public databases such as GEO and SRA;
2. Association between genetic variants in mRNA modification (writer, eraser, and reader genes) and human cancers, especially rare variants or somatic mutations or rare copy number variations occurred in mRNA modification gene regions. We welcome the pheWAS study based on large population cohorts such as UK-biobank, eMERGE to identify interesting genetics association between m6A/m1A systems with complex human diseases with large phenotypes;
3. Genetic and epigenetic regulations of mRNA modification proteins (writer, eraser, readers) including identifying eQTLs, TFBS and DNA methylation, histone modification and miRNAs as well as the corresponding interaction on how to transcriptional regulate mRNA modification gene expression;
4. Pathway analysis to show how m6A modification is involved in different disease pathways, especially cancer-related pathways, such as ferroptosis, immune tolerance pathway and epithelial-mesenchymal transition pathway.