Dual effects of N6-methyladenosine on cancer progression and immunotherapy

According to the latest global cancer statistics, cancer has become a major threat to human health, but cancer treatment has encountered many bottlenecks. As an emerging topic in epigenetics, N-6-methyladenosine (m(6)A) is the most common internal modification on eukaryotic mRNA, which has attracted increasing attention in recent years. Accumulating studies have shown that aberrant m(6)A modifications have profound effects on the characteristics of tumors, which undoubtedly led to a significant breakthrough in cancer treatment. Although m(6)A function as an oncogene or tumor suppressor is not fully revealed, determining its precise function in the development and evolution of malignant tumors is crucial in improving clinical decisions involving targeted therapies. In this review, we briefly introduce the composition of the m(6)A methylation machinery and mainly summarize the biological mechanism of m(6)A in cancer cell death, angiogenesis, epithelial-mesenchymal transition (EMT), and therapeutic resistance. Subsequently, we present the exogenous regulatory factors of m(6)A and highlight the role of m(6)A on immune cells and cancer immunotherapy. The potential therapeutic strategies of m(6)A in human cancer are also discussed, considering research gaps and future applications.