Crosstalk among m6A RNA methylation, hypoxia and metabolic reprogramming in TME: from immunosuppressive microenvironment to clinical application

Abstract

The tumor microenvironment (TME), which is regulated by intrinsic oncogenic mechanisms and epigenetic modifications, has become a research hotspot in recent years. Characteristic features of TME include hypoxia, metabolic dysregulation, and immunosuppression. One of the most common RNA modifications, N6-methyladenosine (m6A) methylation, is widely involved in the regulation of physiological and pathological processes, including tumor development. Compelling evidence indicates that m6A methylation regulates transcription and protein expression through shearing, export, translation, and processing, thereby participating in the dynamic evolution of TME. Specifically, m6A methylation-mediated adaptation to hypoxia, metabolic dysregulation, and phenotypic shift of immune cells synergistically promote the formation of an immunosuppressive TME that supports tumor proliferation and metastasis. In this review, we have focused on the involvement of m6A methylation in the dynamic evolution of tumor-adaptive TME and described the detailed mechanisms linking m6A methylation to change in tumor cell biological functions. In view of the collective data, we advocate treating TME as a complete ecosystem in which components crosstalk with each other to synergistically achieve tumor adaptive changes. Finally, we describe the potential utility of m6A methylation-targeted therapies and tumor immunotherapy in clinical applications and the challenges faced, with the aim of advancing m6A methylation research.

An overview of the effects and mechanisms of m6 A methylation on innate immune cells in sepsis

“…YTHDF1 has been reported to promote mRNA translation by binding to m 6 A, while YTHDF1 knockdown leads to a decrease in translation efficiency. YTHDF1 interacts with m 6 A-modified p65 mRNA and facilitates its translation, thereby regulating the inflammatory response ( 17 ). Another study by Zhang et al.…”

Identification of the Expression Patterns and Potential Prognostic Role of m6A-RNA Methylation Regulators in Wilms Tumor

“…A large number of existing studies have shown that the tumor microenvironment can not only in uence tumor cell growth and metastasis, but also has great importance in therapy [39][40][41] , in particular, the association between TME and methylation modi cations and the in uence of TME on tumor progression in WT has been reported 42,43 . We quanti ed the in ltration of 29 different immune cell types in WT samples by ssGSEA analysis.…”

Crosstalk among N6-methyladenosine modification and RNAs in central nervous system injuries

“…The m6A modification-related proteins can act as writers or erasers to add or remove m6A, respectively, that means, these proteins determine whether m6A is methylated or demethylated. While, RBPs called readers recognize m6A sites to interact with RNA ( Zhang F. et al, 2022 ). At present, it has been found that there was abnormal expression of m6A modification regulatory factors in CNS injuries, which may explain their pathological mechanisms ( Figure 1 ).…”