Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown

Abstract Background Telomeric repeat binding factor 2 (TERF2), a key component of the Shelterin complex, is crucial for maintaining telomere integrity and genome stability. While the involvement of TERF2 in tumorigenesis and progression has been documented, comprehensive pan-cancer analyses of TERF2...

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Main Authors: Qiang Ma, Wen Xu, Xiaolan Guo
Format: Article
Language:English
Published: Springer 2025-02-01
Series:Discover Oncology
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Online Access:https://doi.org/10.1007/s12672-025-01954-0
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author Qiang Ma
Wen Xu
Xiaolan Guo
author_facet Qiang Ma
Wen Xu
Xiaolan Guo
author_sort Qiang Ma
collection DOAJ
description Abstract Background Telomeric repeat binding factor 2 (TERF2), a key component of the Shelterin complex, is crucial for maintaining telomere integrity and genome stability. While the involvement of TERF2 in tumorigenesis and progression has been documented, comprehensive pan-cancer analyses of TERF2 across different malignancies remain scarce. Methods In the present study, the expression, mutations, immune cell infiltration, and interacting genes of TERF2 were systematically evaluated through bioinformatics analysis, and in vitro experiments were performed to elucidate the functional roles of TERF2 in gastric cancer. Results The findings revealed that TERF2 was predominantly upregulated in cholangiocarcinoma (CHOL), diffuse large B-cell lymphoma (DLBC), pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and thymoma (THYM), correlating with tumor progression. Amplification and mutations were identified as the primary alterations of TERF2, particularly associated with liver hepatocellular carcinoma (LIHC). Furthermore, TERF2 expression was linked to the infiltration of cancer-associated fibroblasts and immune cells in certain cancer types. Protein–protein interaction (PPI) analysis highlighted several genes associated with TERF2, including CTCF, DDX19A, MATR3, ZFP1, and ZFP90. Additionally, in vitro experiments demonstrated that TERF2 knockdown significantly suppressed the proliferation and migration of gastric cancer cells. Conclusions These results suggest that dysregulation and mutations of TERF2 are prevalent across various cancers, contributing to tumor immunity and acting as an oncogenic factor, thus positioning TERF2 as a potential therapeutic target in cancer treatment.
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spelling doaj-art-e1b5bb2fc3764af582f23936ff5ecd0b2025-08-20T02:16:45ZengSpringerDiscover Oncology2730-60112025-02-0116111510.1007/s12672-025-01954-0Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdownQiang Ma0Wen Xu1Xiaolan Guo2Department of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical CollegeDepartment of Gastroenterology, People’s Hospital of Hechuan DistrictDepartment of Clinical Laboratory, Affiliated Hospital of North Sichuan Medical CollegeAbstract Background Telomeric repeat binding factor 2 (TERF2), a key component of the Shelterin complex, is crucial for maintaining telomere integrity and genome stability. While the involvement of TERF2 in tumorigenesis and progression has been documented, comprehensive pan-cancer analyses of TERF2 across different malignancies remain scarce. Methods In the present study, the expression, mutations, immune cell infiltration, and interacting genes of TERF2 were systematically evaluated through bioinformatics analysis, and in vitro experiments were performed to elucidate the functional roles of TERF2 in gastric cancer. Results The findings revealed that TERF2 was predominantly upregulated in cholangiocarcinoma (CHOL), diffuse large B-cell lymphoma (DLBC), pancreatic adenocarcinoma (PAAD), stomach adenocarcinoma (STAD), and thymoma (THYM), correlating with tumor progression. Amplification and mutations were identified as the primary alterations of TERF2, particularly associated with liver hepatocellular carcinoma (LIHC). Furthermore, TERF2 expression was linked to the infiltration of cancer-associated fibroblasts and immune cells in certain cancer types. Protein–protein interaction (PPI) analysis highlighted several genes associated with TERF2, including CTCF, DDX19A, MATR3, ZFP1, and ZFP90. Additionally, in vitro experiments demonstrated that TERF2 knockdown significantly suppressed the proliferation and migration of gastric cancer cells. Conclusions These results suggest that dysregulation and mutations of TERF2 are prevalent across various cancers, contributing to tumor immunity and acting as an oncogenic factor, thus positioning TERF2 as a potential therapeutic target in cancer treatment.https://doi.org/10.1007/s12672-025-01954-0Telomeric repeat binding factor 2TERF2Bioinformatics analysisGastric cancer
spellingShingle Qiang Ma
Wen Xu
Xiaolan Guo
Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown
Discover Oncology
Telomeric repeat binding factor 2
TERF2
Bioinformatics analysis
Gastric cancer
title Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown
title_full Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown
title_fullStr Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown
title_full_unstemmed Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown
title_short Pan‑cancer analysis of the oncogenic role of telomeric repeat binding factor 2 (TERF2) in human tumors and in vitro validation in gastric cancer by TERF2 knockdown
title_sort pan cancer analysis of the oncogenic role of telomeric repeat binding factor 2 terf2 in human tumors and in vitro validation in gastric cancer by terf2 knockdown
topic Telomeric repeat binding factor 2
TERF2
Bioinformatics analysis
Gastric cancer
url https://doi.org/10.1007/s12672-025-01954-0
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