研究动态
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乳腺癌中端粒酶逆转录酶(TERT/hTERT)的调控和临床潜力。

Regulation and clinical potential of telomerase reverse transcriptase (TERT/hTERT) in breast cancer.

发表日期:2023 Aug 23
作者: Ruozhu Yang, Yi Han, Xinyu Guan, Yue Hong, Jiahao Meng, Shirong Ding, Qian Long, Wenjun Yi
来源: Cellular & Molecular Immunology

摘要:

端粒酶逆转录酶(TERT/hTERT)作为端粒酶的中心催化亚基,是维持端粒和人类基因组稳定性的关键酶。 hTERT的高活化在超过90%的肿瘤中观察到,并在肿瘤的起始和进展中发挥重要作用。对癌症中hTERT活化机制的深入探索对于推进我们对疾病的理解和开发更有效的治疗策略具有潜力。在乳腺癌中,hTERT的表达受到表观遗传、转录、后转录修饰机制和DNA变异的调控。除了在端粒维持中的经典功能外,hTERT通过端粒酶非依赖机制发挥非经典作用,促进疾病进展。本综述总结了在乳腺癌中调控hTERT的机制,并阐明其活化的功能意义。鉴于hTERT在大多数乳腺癌细胞中的过表达情况,检测hTERT及其相关分子可提升乳腺癌的早期筛查和预后评估水平。虽然仍处于早期阶段,但针对hTERT及其调控分子的治疗方法显示出作为乳腺癌治疗可行策略的希望。本文还讨论了这些方法。视频摘要。© 2023. BioMed Central Ltd., part of Springer Nature.
Telomerase reverse transcriptase (TERT/hTERT) serves as the pivotal catalytic subunit of telomerase, a crucial enzyme responsible for telomere maintenance and human genome stability. The high activation of hTERT, observed in over 90% of tumors, plays a significant role in tumor initiation and progression. An in-depth exploration of hTERT activation mechanisms in cancer holds promise for advancing our understanding of the disease and developing more effective treatment strategies. In breast cancer, the expression of hTERT is regulated by epigenetic, transcriptional, post-translational modification mechanisms and DNA variation. Besides its canonical function in telomere maintenance, hTERT exerts non-canonical roles that contribute to disease progression through telomerase-independent mechanisms. This comprehensive review summarizes the regulatory mechanisms governing hTERT in breast cancer and elucidates the functional implications of its activation. Given the overexpression of hTERT in most breast cancer cells, the detection of hTERT and its associated molecules are potential for enhancing early screening and prognostic evaluation of breast cancer. Although still in its early stages, therapeutic approaches targeting hTERT and its regulatory molecules show promise as viable strategies for breast cancer treatment. These methods are also discussed in this paper. Video Abstract.© 2023. BioMed Central Ltd., part of Springer Nature.