The evolving landscape of N6-methyladenosine modification in the tumor microenvironment

The tumor microenvironment (TME), controlled by intrinsic mechanisms of carcinogenesis and epigenetic modifications, has, in recent years, become a heavily researched topic. The TME can be described in terms of hypoxia, metabolic dysregulation, immune escape, and chronic inflammation. RNA methylation, an epigenetic modification, has recently been found to have a pivotal role in shaping the TME. The N-6-methylation of adenosine (m(6)A) modification is the most common type of RNA methylation that occurs in the N-6-position of adenosine, which is the primary internal modification of eukaryotic mRNA. Compelling evidence has demonstrated that m6A regulates transcriptional and protein expression through splicing, translation, degradation, and export, thereby mediating the biological processes of cancer cells and/or stromal cells and characterizing the TME. The TME also has a crucial role in the complicated regulatory network of m(6)A modifica-tions and, subsequently, influences tumor initiation, progression, and therapy responses. In this review, we describe the features of the TME and how the m(6)A modification modulates and interacts with it. We also focus on various factors and pathways involved in m(6)A methylation. Finally, we discuss potential therapeutic strategies and prognostic biomarkers with respect to the TME and m6A modification.