Laboratory of Medical Investigation (LIM55), Urology Department, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; D'Or Institute for Research and Education (IDOR), Sao Paulo, Brazil.
Laboratory of Medical Investigation (LIM55), Urology Department, Faculdade de Medicina FMUSP, Universidade de Sao Paulo, Sao Paulo, Brazil; Minas Gerais State University (UEMG), Passos, Minas Gerais, Brazil.
Cancer Genet. 2022 Apr;262-263:80-90. doi: 10.1016/j.cancergen.2022.01.006. Epub 2022 Feb 1.
Telomere dysfunction is one of the hallmarks of cancer, which puts telomere-associated genes in a prominent position in oncology. The CTC1-STN1-TEN1 (CST) complex is vital for telomere maintenance and participates in several steps of DNA metabolism, such as repair and replication, essential functions for malignant cells. Despite this, little is known about these genes in cancer biology. Here, using bioinformatics tools, we performed a study in 33 cancer types and over 10,000 TCGA samples analyzing the role of the CST complex in cancer. We obtained the somatic landscape and gene expression patterns of each of the subunits of the complex studied. Furthermore, we show that CST is important for genetic stability and nucleic acid metabolism in cancer. We identify possible interactors, transcription factors, and microRNAs associated with CST and two drugs that may disrupt their pathways. In addition, we show that CST gene expression is associated with cancer survival and recurrence in several tumor types. Finally, we show negative and positive correlations between immune checkpoint genes and CST in different types of cancer. With this work, we corroborate the importance of these genes in cancer biology and open perspectives for their use in other works in the field.
端粒功能障碍是癌症的标志之一,这使得端粒相关基因在肿瘤学中处于突出地位。CTC1-STN1-TEN1(CST)复合物对于端粒的维持至关重要,并参与 DNA 代谢的多个步骤,如修复和复制,这些都是恶性细胞的基本功能。尽管如此,人们对这些基因在癌症生物学中的作用知之甚少。在这里,我们使用生物信息学工具,在 33 种癌症类型和超过 10000 个 TCGA 样本中进行了研究,分析了 CST 复合物在癌症中的作用。我们获得了所研究复合物每个亚基的体细胞景观和基因表达模式。此外,我们表明 CST 对于癌症中的遗传稳定性和核酸代谢很重要。我们确定了与 CST 相关的可能相互作用蛋白、转录因子和 microRNAs ,以及两种可能破坏其途径的药物。此外,我们表明 CST 基因表达与几种肿瘤类型的癌症生存和复发有关。最后,我们表明在不同类型的癌症中,免疫检查点基因与 CST 之间存在负相关和正相关。通过这项工作,我们证实了这些基因在癌症生物学中的重要性,并为它们在该领域的其他工作中的应用开辟了前景。
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