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Diagnostic and therapeutic value of nonsense-mediated mRNA decay in cancer
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Abstract:
Nonsense-mediated mRNA decay (NMD) serves as a quality control mechanism, degrading aberrant mRNAs with premature termination codons (PTCs). It also plays a role in growth and development, immune regulation, and is closely associated with the tumor microenvironment. NMD has a dual role in cancer; on the one hand, it inhibits tumor progression through down-regulation of pro-oncogenic protein expression, inhibition of pro-oncogenic signaling pathways and stressful microenvironments, while one the other hand, it promotes tumor progression by inhibiting oncogene expression, cancer cell apoptosis and tumor neoantigen production. Notably, NMD does not degrade all PTC-containing mRNAs. The location of the PTC may determine whether NMD is triggered or evaded. Since different genes vary greatly in high-frequency mutation regions, the likelihood of triggering NMD after a PTC mutation differs across genes. With the maturation and widespread use of second-generation sequencing technology, gene mutation screening has become a routine clinical diagnostic tool, making it possible to explore the patterns and significance of NMD from a multi-gene perspective. By further understanding the functions and mechanisms of NMD and assessing the NMD levels through high-throughput sequencing and computational algorithms, its potential clinical value is expected to be revealed, contributing to the advancement of personalized treatment and precision medicine.
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