N6-methyladenosine (m6A) as a regulator of carcinogenesis and drug resistance by targeting epithelial-mesenchymal transition and cancer stem cells

Emergence of drug resistance to chemotherapeutic agents is the principal obstacle towards curative cancer treatment in human cancer patients. It is in an urgent to explore the underlying molecular mechanisms to overcome the drug resistance. N6-Methyladenosine (m6A) RNA modification is the most abundant reversible RNA modification and has emerged in recent years to regulate gene expression in eukaryotes. Recent evidence has identified m6A is associated with cancer pathogenesis and drug resistance, contributing to the self-renewal and differentiation of cancer stem cell, tumor epithelial-mesenchymal transition (EMT) and tumor metastasis. Here we reviewed up-to-date knowledge of the relationship between m6A modulation and drug resistance. Furthermore, we illustrated the underlying mechanisms of m6A modulation in drug resistance. Lastly, we discussed the regulation of m6A modulation in EMT and cancer stem cells. Hence, it will help to provide significant therapeutic strategies to overcome drug resistance for cancer patients by changing m6A-related proteins via targeting cancer stem cells and EMT-phenotypic cells.

Automated summary

The emergence of drug resistance is a major obstacle in curative cancer treatment. Exploring the molecular mechanisms behind drug resistance, particularly the role of N6-Methyladenosine (m6A) RNA modification, is crucial. Recent evidence has shown that m6A is associated with cancer pathogenesis and drug resistance, impacting cancer stem cell self-renewal, tumor epithelial-mesenchymal transition (EMT), and metastasis. This review provides an overview of the relationship between m6A modulation and drug resistance, discussing the underlying mechanisms and its regulation in EMT and cancer stem cells. Targeting m6A-related proteins to address drug resistance in cancer patients offers significant therapeutic strategies.