Department of Virology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Faculti of Medicine, Golestan University of Medical sciences, Golestan, Iran.
Cancer Treat Res Commun. 2021;27:100323. doi: 10.1016/j.ctarc.2021.100323. Epub 2021 Jan 27.
Human telomerase reverse transcriptase (hTERT) is an enzyme that is critically involved in elongating and maintaining telomeres length to control cell life span and replicative potential. Telomerase activity is continuously expressed in human germ-line cells and most cancer cells, whereas it is suppressed in most somatic cells. In normal cells, by reducing telomerase activity and progressively shortening the telomeres, the cells progress to the senescence or apoptosis process. However, in cancer cells, telomere lengths remain constant due to telomerase's reactivation, and cells continue to proliferate and inhibit apoptosis, and ultimately lead to cancer development and human death due to metastasis. Studies demonstrated that several DNA and RNA oncoviruses could interact with telomerase by integrating their genome sequence within the host cell telomeres specifically. Through the activation of the hTERT promoter and lengthening the telomere, these cells contributes to cancer development. Since oncoviruses can activate telomerase and increase hTERT expression, there are several therapeutic strategies based on targeting the telomerase of cancer cells like telomerase-targeted peptide vaccines, hTERT-targeting dendritic cells (DCs), hTERT-targeting gene therapy, and hTERT-targeting CRISPR/Cas9 system that can overcome tumor-mediated toleration mechanisms and specifically apoptosis in cancer cells. This study reviews available data on the molecular structure of telomerase and the role of oncoviruses and telomerase interaction in cancer development and telomerase-dependent therapeutic approaches to conquest the cancer cells.
人类端粒酶逆转录酶（hTERT）是一种酶，它在延长和维持端粒长度方面起着至关重要的作用，以控制细胞寿命和复制潜能。端粒酶活性在人类生殖细胞和大多数癌细胞中持续表达，而在大多数体细胞中则受到抑制。在正常细胞中，通过降低端粒酶活性和逐渐缩短端粒，细胞进入衰老或凋亡过程。然而，在癌细胞中，由于端粒酶的重新激活，端粒长度保持不变，细胞继续增殖并抑制凋亡，最终导致癌症发展和人类因转移而死亡。研究表明，几种 DNA 和 RNA 致癌病毒可以通过将其基因组序列整合到宿主细胞的端粒中，与端粒酶相互作用。通过激活 hTERT 启动子和延长端粒，这些细胞有助于癌症的发展。由于致癌病毒可以激活端粒酶并增加 hTERT 的表达，因此有几种基于针对癌细胞端粒酶的治疗策略，如端粒酶靶向肽疫苗、hTERT 靶向树突状细胞（DCs）、hTERT 靶向基因治疗和 hTERT 靶向 CRISPR/Cas9 系统，可以克服肿瘤介导的耐受机制并特异性诱导癌细胞凋亡。本研究综述了端粒酶的分子结构以及致癌病毒与端粒酶相互作用在癌症发展中的作用，以及基于端粒酶的治疗方法征服癌细胞的研究进展。
