Fernandes Stina George, Dsouza Rebecca, Pandya Gouri, Kirtonia Anuradha, Tergaonkar Vinay, Lee Sook Y, Garg Manoj, Khattar Ekta
Sunandan Divatia School of Science, SVKM's NMIMS (Deemed to be University), Vile Parle West, Mumbai 400056, India.
Amity Institute of Molecular Medicine and Stem Cell Research (AIMMSCR), Amity University Uttar Pradesh, Noida 201313, India.
Cancers (Basel). 2020 Jul 14;12(7):1901. doi: 10.3390/cancers12071901.
Telomeres are the ends of linear chromosomes comprised of repetitive nucleotide sequences in humans. Telomeres preserve chromosomal stability and genomic integrity. Telomere length shortens with every cell division in somatic cells, eventually resulting in replicative senescence once telomere length becomes critically short. Telomere shortening can be overcome by telomerase enzyme activity that is undetectable in somatic cells, while being active in germline cells, stem cells, and immune cells. Telomeres are bound by a shelterin complex that regulates telomere lengthening as well as protects them from being identified as DNA damage sites. Telomeres are transcribed by RNA polymerase II, and generate a long noncoding RNA called telomeric repeat-containing RNA (TERRA), which plays a key role in regulating subtelomeric gene expression. Replicative immortality and genome instability are hallmarks of cancer and to attain them cancer cells exploit telomere maintenance and telomere protection mechanisms. Thus, understanding the role of telomeres and their associated proteins in cancer initiation, progression and treatment is very important. The present review highlights the critical role of various telomeric components with recently established functions in cancer. Further, current strategies to target various telomeric components including human telomerase reverse transcriptase (hTERT) as a therapeutic approach in human malignancies are discussed.
端粒是人类线性染色体的末端，由重复的核苷酸序列组成。端粒维持染色体稳定性和基因组完整性。在体细胞中，每次细胞分裂端粒长度都会缩短，一旦端粒长度变得极短，最终会导致复制性衰老。端粒缩短可通过端粒酶活性来克服，端粒酶在体细胞中无法检测到，但在生殖细胞、干细胞和免疫细胞中具有活性。端粒由一个端粒保护蛋白复合体结合，该复合体调节端粒延长，并保护它们不被识别为DNA损伤位点。端粒由RNA聚合酶II转录，并产生一种名为端粒重复序列含RNA（TERRA）的长链非编码RNA，它在调节亚端粒基因表达中起关键作用。复制永生和基因组不稳定是癌症的标志，为了实现这些，癌细胞利用端粒维持和端粒保护机制。因此，了解端粒及其相关蛋白在癌症发生、发展和治疗中的作用非常重要。本综述强调了各种具有最近确定功能的端粒成分在癌症中的关键作用。此外，还讨论了针对包括人端粒酶逆转录酶（hTERT）在内的各种端粒成分作为人类恶性肿瘤治疗方法的当前策略。
