Progress of research on m6A demethylases in gastric cancer / 上海交通大学学报（医学版）

ABSTRACT

Gastric cancer(GC)is one of the most common malignancies in the digestive system.Many patients are found in advanced stage and have a poor prognosis.Surgery and chemotherapy remain the main treatments for gastric cancer.N6-methyladenosine(m6A)is a hot topic in tumor research in recent years.As the most common form of RNA modification in eukaryotes,m6A can regulate various stages of the RNA cycle,including RNA splicing,processing,degradation,and translation,thereby regulating RNA expression and function,playing a critical role in various pathways such as cell differentiation,development,and metabolism.The m6A demethylase can remove methyl groups on RNA,ensuring that m6A methylation is a dynamic and reversible process.As a key enzyme in the m6A methylation process,the imbalance of m6A demethylases fat mass and obesity-associated protein(FTO),AlkB homolog 5(ALKBH5)and ALKBH3 regulate the progression of gastric cancer through various mechanisms,which is closely related to the occurrence and development of gastric cancer.These m6A demethylases regulate the signaling pathway,alter the proliferation and invasion ability of gastric cancer cells,affect its resistance to chemotherapy drugs,participate in regulating the immune response and mitochondrial metabolism of gastric cancer,and affect the growth of gastric cancer cells.They are expected to become a novel therapeutic target.This article comprehensively summarizes the molecular mechanism of m6A demethylase involved in the occurrence and development of gastric cancer,and the relationship between its expression and function,and biological characteristics of m6A demethylase were reviewed,aiming to provide new research ideas for early diagnosis and targeted treatment of gastric cancer.