ORIGINAL RESEARCH article
Front. Oncol.
Sec. Gastrointestinal Cancers: Colorectal Cancer
Volume 15 - 2025 | doi: 10.3389/fonc.2025.1593107
This article is part of the Research TopicMetabolic Cell Death in Cancer: Innovative Therapeutic Avenues for Cancer TreatmentView all articles
Bioinformatics and Experimental Unveiling of TIMP1 as a Novel Therapeutic Target in Colorectal Cancer Ferroptosis
Provisionally accepted
Chao Tang1
Zhenhan Li2
Tianyu Song1Linming Lu2Bofeng Chen2Tao Zhang2Yi Zhang2Jianle Lao3*Jie Yang4*
Hao Chen2*- 1Nanjing University of Chinese Medicine, Nanjing, China
- 2Wannan Medical College, Wuhu, Anhui Province, China
- 3Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, Guangx, China
- 4Nanjing Drum Tower Hospital, Nanjing, Jiangsu Province, China
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Colorectal cancer (CRC) remains a globally prevalent and lethal malignancy, with ferroptosis emerging as a novel cell death mechanism. This study aimed to elucidate the role of key genes in ferroptosis regulation and their impact on CRC malignancy. Using bioinformatics and experimental methods, we identified TIMP1 as an oncogene that may promote CRC progression via ferroptosis, a pathway implicated in diverse diseases. TIMP1 expression was analyzed in TCGA CRC datasets and validated using the UALCAN database. Results confirmed TIMP1 as a critical ferroptosisrelated gene in CRC, with elevated expression correlating with advanced pathological staging.Immunohistochemistry demonstrated significantly higher TIMP1 levels in CRC tissues compared to healthy controls. Functional assays revealed that TIMP1 knockdown enhanced ferroptosis sensitivity, suppressed CRC cell proliferation and migration, and reduced expression of ferroptosis regulators GPX4 and SLC7A11. Collectively, these findings indicate that TIMP1 drives CRC malignancy through ferroptosis modulation, positioning TIMP1 as a potential therapeutic target and offering novel insights for CRC-targeted therapies.
Keywords: colorectal cancer, ferroptosis, TIMP1, Tumor malignancy, Therapeutic target
Received: 13 Mar 2025; Accepted: 17 Jun 2025.
Copyright: © 2025 Tang, Li, Song, Lu, Chen, Zhang, Zhang, Lao, Yang and Chen. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
* Correspondence:
Jianle Lao, Affiliated Hospital of Youjiang Medical University for Nationalities, Baise, 533000, Guangx, China
Jie Yang, Nanjing Drum Tower Hospital, Nanjing, 210008, Jiangsu Province, China
Hao Chen, Wannan Medical College, Wuhu, 241002, Anhui Province, China
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