无义介导的mRNA降解（NMD）作为一种质量控制机制，可降解含有过早终止密码子（PTC）的异常mRNA，参与生长 发育、调节免疫功能，且与肿瘤微环境密切相关。NMD对肿瘤有抑制或促进的双重作用：一方面，NMD通过下调促癌蛋白表达、 抑制促癌信号通路和应激微环境等途径抑制肿瘤进展；另一方面，NMD通过抑制抑癌基因的表达、癌细胞凋亡和肿瘤新抗原的 产生促进肿瘤进展。此外，NMD并非降解所有携带PTC的mRNA，PTC出现的位置可能决定NMD触发或逃逸，由于各基因的高 频突变区域各不相同，因此不同基因发生PTC突变后是否触发NMD则具有不同的倾向性。随着二代测序技术的成熟与普及，基 因突变筛查已成为临床诊疗常规手段，这使得从多基因层面探究NMD的规律与意义成为可能。因此，在进一步了解NMD的功 能及其机制的基础上，通过高通量测序与计算机算法评估NMD水平，有望在临床工作中扬长避短地发挥NMD潜在的临床价值， 助力个性化临床诊治与精准医疗的发展。

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.

国家自然科学基金面上项目（No. 82173198；No. 81872143）