BACKGROUND

N6-methyladenosine (mA) RNA methylation modifications have been widely implicated in the metabolic reprogramming of various cell types within the tumor microenvironment (TME) and are essential for meeting the demands of cellular growth and maintaining tissue homeostasis, enabling cells to adapt to the specific conditions of the TME. An increasing number of research studies have focused on the role of mA modifications in glucose, amino acid and lipid metabolism, revealing their capacity to induce aberrant changes in metabolite levels. These changes may in turn trigger oncogenic signaling pathways, leading to substantial alterations within the TME. Notably, certain metabolites, including lactate, succinate, fumarate, 2-hydroxyglutarate (2-HG), glutamate, glutamine, methionine, S-adenosylmethionine, fatty acids and cholesterol, exhibit pronounced deviations from normal levels. These deviations not only foster tumorigenesis, proliferation and angiogenesis but also give rise to an immunosuppressive TME, thereby facilitating immune evasion by the tumor.

AIM OF REVIEW

The primary objective of this review is to comprehensively discuss the regulatory role of mA modifications in the aforementioned metabolites and their potential impact on the development of an immunosuppressive TME through metabolic alterations.

KEY SCIENTIFIC CONCEPTS OF REVIEW

This review aims to elaborate on the intricate networks governed by the mA-metabolite-TME axis and underscores its pivotal role in tumor progression. Furthermore, we delve into the potential implications of the mA-metabolite-TME axis for the development of novel and targeted therapeutic strategies in cancer research.