Nonsense-mediated mRNA decay: a key regulatory system engaged in cancer

Nonsense-mediated mRNA decay (NMD) is a critical cellular surveillance mechanism that prevents the translation of defective or deleterious proteins. The regulation of NMD, including both its activation and the evasion of its target mRNA, is intricately linked to tumorigenesis. When NMD becomes overactivated, it can downregulate tumor suppressor transcripts, or eliminate immunogenic peptides, thereby promoting tumor growth and immune evasion. In contrast, reduced or defective NMD can stabilize mutated oncogene transcripts and drive tumor progression. This review provides a comprehensive overview of the physiological mechanisms of NMD, its diverse substrate features, and its regulatory dynamics. We further focus on recent advances in clarifying the interplay between NMD and tumor biology. By integrating the current findings, we aim to provide an insightful understanding of how NMD contributes to tumor initiation, tumor progression, and immune modulation.