Institute of Biomedical and Genetic Engineering (IBGE), Islamabad 44000, Pakistan.
Regenerative Medicine Laboratory, Faculty of Medicine, Saint-Joseph University, Beirut 1107-2180, Lebanon.
Int J Mol Sci. 2018 Apr 1;19(4):1051. doi: 10.3390/ijms19041051.
Substantial fraction of high-quality information is continuously being added into the existing pool of knowledge related to the biology of telomeres. Based on the insights gleaned from decades of research, it is clear that chromosomal stability needs a highly controlled and dynamic balance of DNA gain and loss in each terminal tract of telomeric repeats. Telomeres are formed by tandem repeats of TTAGGG sequences, which are gradually lost with each round of division of the cells. Targeted inhibition of telomerase to effectively induce apoptosis in cancer cells has attracted tremendous attention and overwhelmingly increasingly list of telomerase inhibitors truthfully advocates pharmacological significance of telomerase. Telomerase reverse transcriptase (TERT) is a multi-talented and catalytically active component of the telomerase-associated protein machinery. Different proteins of telomerase-associated machinery work in a synchronized and orchestrated manner to ensure proper maintenance of telomeric length of chromosomes. Rapidly emerging scientific findings about regulation of TERT by microRNAs has revolutionized our understanding related to the biology of telomeres and telomerase. In this review, we have comprehensively discussed how different miRNAs regulate TERT in different cancers. Use of miRNA-based therapeutics against TERT in different cancers needs detailed research in preclinical models for effective translation of laboratory findings to clinically effective therapeutics.
大量高质量的信息不断被添加到与端粒生物学相关的现有知识库中。根据数十年研究中获得的见解，很明显，染色体稳定性需要在端粒重复的每个末端片段中对 DNA 的增益和损耗进行高度控制和动态平衡。端粒由 TTAGGG 序列的串联重复组成，随着细胞的每一轮分裂，这些序列逐渐丢失。靶向抑制端粒酶以有效诱导癌细胞凋亡引起了极大的关注，越来越多的端粒酶抑制剂清单真实地证明了端粒酶的药理学意义。端粒酶逆转录酶（TERT）是端粒酶相关蛋白机器的多功能和催化活性成分。端粒酶相关机器的不同蛋白以同步和协调的方式协同工作，以确保染色体端粒长度的适当维持。关于 microRNA 对 TERT 的调节的迅速出现的科学发现彻底改变了我们对端粒和端粒酶生物学的理解。在这篇综述中，我们全面讨论了不同的 microRNA 如何在不同的癌症中调节 TERT。在临床前模型中需要对针对不同癌症的 TERT 的基于 microRNA 的治疗进行详细研究，以便将实验室发现有效地转化为临床有效的治疗方法。
