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泛癌症分析显示 CTC1-STN1-TEN1(CST)复合物在肿瘤学中可能具有关键地位。

Pan-cancer analysis reveals that CTC1-STN1-TEN1 (CST) complex may have a key position in oncology.

机构信息

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.

出版信息

Cancer Genet. 2022 Apr;262-263:80-90. doi: 10.1016/j.cancergen.2022.01.006. Epub 2022 Feb 1.


DOI:10.1016/j.cancergen.2022.01.006
PMID:35134616
Abstract

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.

摘要

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。

相似文献

[1]
Pan-cancer analysis reveals that CTC1-STN1-TEN1 (CST) complex may have a key position in oncology.

Cancer Genet. 2022-4

[2]
CTC1-STN1 terminates telomerase while STN1-TEN1 enables C-strand synthesis during telomere replication in colon cancer cells.

Nat Commun. 2018-7-19

[3]
Human TEN1 maintains telomere integrity and functions in genome-wide replication restart.

J Biol Chem. 2013-9-11

[4]
POT1a and components of CST engage telomerase and regulate its activity in Arabidopsis.

PLoS Genet. 2014-10-16

[5]
CTC1 OB-B interaction with TPP1 terminates telomerase and prevents telomere overextension.

Nucleic Acids Res. 2023-6-9

[6]
The human CTC1/STN1/TEN1 complex regulates telomere maintenance in ALT cancer cells.

Exp Cell Res. 2017-6-15

[7]
Tpz1TPP1 SUMOylation reveals evolutionary conservation of SUMO-dependent Stn1 telomere association.

EMBO Rep. 2014-8

[8]
Upregulation of shelterin and CST genes and longer telomeres are associated with unfavorable prognostic characteristics in prostate cancer.

Cancer Genet. 2024-6

[9]
Human CST has independent functions during telomere duplex replication and C-strand fill-in.

Cell Rep. 2012-11-8

[10]
Human CST abundance determines recovery from diverse forms of DNA damage and replication stress.

Cell Cycle. 2014

引用本文的文献

[1]
Suppression of CTC1 inhibits hepatocellular carcinoma cell growth and enhances RHPS4 cytotoxicity.

Mol Biol Rep. 2024-7-13

[2]
Conditional Depletion of STN1 in Mouse Embryonic Fibroblasts.

Bio Protoc. 2024-4-20

[3]
CaMKK2 and CHK1 phosphorylate human STN1 in response to replication stress to protect stalled forks from aberrant resection.

Nat Commun. 2023-11-30

[4]
A novel mutation of CTC1 leads to telomere shortening in a chinese family with interstitial lung disease.

Hereditas. 2023-11-18

[5]
Interactions between the DNA Damage Response and the Telomere Complex in Carcinogenesis: A Hypothesis.

Curr Issues Mol Biol. 2023-9-19

[6]
Deficiency in mammalian STN1 promotes colon cancer development via inhibiting DNA repair.

Sci Adv. 2023-5-10

[7]
Pan-Cancer Analyses Identify the CTC1-STN1-TEN1 Complex as a Protective Factor and Predictive Biomarker for Immune Checkpoint Blockade in Cancer.

Front Genet. 2022-3-16

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