端粒酶反转录酶在肿瘤发生和发展中的作用机制

Effects and underlying mechanisms of telomerase reverse transcriptase in carcinogenesis and cancer progression

端粒酶反转录酶(telomerase reverse transcriptase,TERT)是端粒酶活性的限制因子,通过维持端粒长度控制细胞的衰老及凋亡。TERT在大多数正常细胞中不表达或仅有少量表达,但在肿瘤细胞中的表达升高,对于维持肿瘤细胞的无限复制能力有重要作用。本文综述了调控TERT表达的主要转录因子家族、单核苷酸多态性位点以及DNA甲基化、组蛋白修饰和非编码RNA等表观遗传修饰改变;讨论了上述分子事件在肿瘤发生和发展中的作用;总结了重要的TERT单碱基变异及病毒整合变异;在此基础上讨论了其在肿瘤诊断和预后中的应用。

As a limiting factor in telomerase activity,telomerase reverse transcriptase(TERT)controls cellular senescence and apoptosis by maintaining telomere length.TERT is not expressed or little expressed in most normal cells.However,the abnormal overexpression of TERT promotes the ability of tumor cells to replicate indefinitely.This review summarizes the regulatory mechanisms of TERT expression,including the main transcription factor families,single nucleotide polymorphism sites,and epigenetic modification changes such as DNA methylation,histone modification,and non-coding RNA.The role of these molecular mechanisms as well as significant TERT single-base variants and virus integration variants in the occurrence and development of cancer are reviewed.On this basis,its application in tumor diagnosis and prognosis is discussed.