Bhari Vikas Kumar, Kumar Durgesh, Kumar Surendra, Mishra Rajeev
Department of Biosciences, Manipal University Jaipur, Rajasthan, India.
Department of Physiology, Government Medical College, Kannauj, Uttar Pradesh, India.
Biochem Biophys Rep. 2021 Feb 2;26:100937. doi: 10.1016/j.bbrep.2021.100937. eCollection 2021 Jul.
Telomere encompasses a (TTAGGG)n tandem repeats, and its dysfunction has emerged as the epicenter of driving carcinogenesis by promoting genetic instability. Indeed, they play an essential role in stabilizing chromosomes and therefore protecting them from end-to-end fusion and DNA degradation. Telomere length homeostasis is regulated by several key players including shelterin complex genes, telomerase, and various other regulators. Targeting these regulatory players can be a good approach to combat cancer as telomere length is increasingly correlated with cancer initiation and progression. In this review, we have aimed to describe the telomere length regulator's role in prognostic significance and important drug targets in breast cancer. Moreover, we also assessed alteration in telomeric function by various telomere length regulators and compares this to the regulatory mechanisms that can be associated with clinical biomarkers in cancer. Using publicly available software we summarized mutational and CpG island prediction analysis of the TERT gene breast cancer patient database. Studies have reported that the TERT gene has prognostic significance in breast cancer progression however mechanistic approaches are not defined yet. Interestingly, we reported using the UCSC Xena web-based tool, we confirmed a positive correlation of shelterin complex genes TERF1 and TERF2 in recurrent free survival, indicating the critical role of these genes in breast cancer prognosis. Moreover, the epigenetic landscape of DNA damage repair genes in different breast cancer subtypes also being analyzed using the UCSC Xena database. Together, these datasets provide a comprehensive resource for shelterin complex gene profiles and define epigenetic landscapes of DNA damage repair genes which reveals the key role of shelterin complex genes in breast cancer with the potential to identify novel and actionable targets for treatment.
端粒包含（TTAGGG）n串联重复序列，其功能障碍已成为通过促进基因不稳定驱动致癌作用的核心。事实上，它们在稳定染色体方面发挥着至关重要的作用，从而保护染色体免于端对端融合和DNA降解。端粒长度稳态由包括端粒保护蛋白复合体基因、端粒酶和各种其他调节因子在内的几个关键参与者调节。由于端粒长度与癌症的发生和进展越来越相关，针对这些调节参与者可能是对抗癌症的一种好方法。在这篇综述中，我们旨在描述端粒长度调节因子在乳腺癌预后意义和重要药物靶点中的作用。此外，我们还评估了各种端粒长度调节因子对端粒功能的改变，并将其与癌症中可能与临床生物标志物相关的调节机制进行比较。使用公开可用的软件，我们总结了乳腺癌患者数据库中TERT基因的突变和CpG岛预测分析。研究报告称，TERT基因在乳腺癌进展中具有预后意义，但尚未确定其机制方法。有趣的是，我们报告使用基于UCSC Xena网络的工具，证实了端粒保护蛋白复合体基因TERF1和TERF2在无复发生存中的正相关，表明这些基因在乳腺癌预后中的关键作用。此外，还使用UCSC Xena数据库分析了不同乳腺癌亚型中DNA损伤修复基因的表观遗传格局。总之，这些数据集为端粒保护蛋白复合体基因谱提供了全面的资源，并定义了DNA损伤修复基因的表观遗传格局，揭示了端粒保护蛋白复合体基因在乳腺癌中的关键作用，有可能识别新的可操作治疗靶点。
