Insights into N6-methyladenosine (m6A) modification of noncoding RNA in tumor microenvironment

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes, and it participates in the regulation of pathophysiological processes in various diseases, including malignant tumors, by regulating the expression and function of both coding and non-coding RNAs (ncRNAs). More and more studies demonstrated that m6A modification regulates the production, stability, and degradation of ncRNAs and that ncRNAs also regulate the expression of m6A-related proteins. Tumor microenvironment (TME) refers to the internal and external environment of tumor cells, which is composed of numerous tumor stromal cells, immune cells, immune factors, and inflammatory factors that are closely related to tumors occurrence and development. Recent studies have suggested that crosstalk between m6A modifications and ncRNAs plays an important role in the biological regulation of TME. In this review, we summarized and analyzed the effects of m6A modification-associated ncRNAs on TME from various perspectives, including tumor proliferation, angiogenesis, invasion and metastasis, and immune escape. Herein, we showed that m6A-related ncRNAs can not only be expected to become detection markers of tumor tissue samples, but can also be wrapped into exosomes and secreted into body fluids, thus exhibiting potential as markers for liquid biopsy. This review provides a deeper understanding of the relationship between m6A-related ncRNAs and TME, which is of great significance to the development of a new strategy for precise tumor therapy.

Automated summary

N6-methyladenosine (m6A) is the most abundant RNA modification in eukaryotes and plays a role in regulating pathophysiological processes in various diseases. Studies have shown that m6A modification regulates the production and stability of non-coding RNAs (ncRNAs), which in turn regulate expression of m6A-related proteins. The tumor microenvironment (TME), consisting of stromal cells, immune cells, and inflammatory factors, is closely related to tumor development. Recent research has identified the importance of the interplay between m6A modifications and ncRNAs in regulating the TME. This review provides a comprehensive analysis of the effects of m6A modification-associated ncRNAs on various aspects of the TME, highlighting their potential as detection markers and liquid biopsy tools.