2. Academic Validation
  3. FADS2 inhibits colorectal cancer cell proliferation by regulating ferroptosis through SLC7A11/GPX4

FADS2 inhibits colorectal cancer cell proliferation by regulating ferroptosis through SLC7A11/GPX4

  • Mol Biol Rep. 2025 Apr 15;52(1):394. doi: 10.1007/s11033-025-10395-5.
Qinghui Yang # 1 2,  Hao Zhang # 1 2,  Jing Luo 1 2,  Hongmei Yu 1 2,  Xiaodi Yang 3 4,  Chen Wang 5 6
Affiliations

Affiliations

  • 1 Department of Oncology, Minhang Branch, Zhongshan Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, China.
  • 2 Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer(SMHC), Minhang Hospital & AHS, Fudan University, Shanghai, China.
  • 3 Department of Oncology, Minhang Branch, Zhongshan Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, China. yxiaodi1986@sina.com.
  • 4 Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer(SMHC), Minhang Hospital & AHS, Fudan University, Shanghai, China. yxiaodi1986@sina.com.
  • 5 Department of Oncology, Minhang Branch, Zhongshan Hospital, Fudan University, No. 170 Xinsong Road, Minhang District, Shanghai, China. wang_c@fudan.edu.cn.
  • 6 Key Laboratory of Whole-Period Monitoring and Precise Intervention of Digestive Cancer(SMHC), Minhang Hospital & AHS, Fudan University, Shanghai, China. wang_c@fudan.edu.cn.
  • # Contributed equally.
PMID: 40232565 DOI: 10.1007/s11033-025-10395-5
Abstract

Background: Colorectal Cancer (CRC) is a leading factor in Cancer mortality globally. Ferroptosis, a regulated cell death described via lipid peroxidation, is crucial in Cancer biology. This study explores the link between Ferroptosis, FADS2, and CRC, focusing on the prognostic significance and therapeutic potential of targeting FADS2.

Methods: The differential expression analysis of the Cancer Genome Atlas-colon adenocarcinoma (TCGA-COAD) and GSE36400 datasets was conducted to determine key ferroptosis-related genes, followed by functional enrichment analysis. Prognosis-related genes were assessed utilizing Least Absolute Shrinkage and Selection Operator (LASSO) COX regression. Genetic variation analysis and immune analysis were employed to evaluate the clinical significance of FADS2. The impacts of FADS2 knockdown on CRC cell migration, proliferation, invasion, and Ferroptosis were evaluated by in vitro cell experiments.

Results: 64 key ferroptosis-related genes in CRC were highly enriched in pathways such as glutathione metabolism and peroxisome. Eleven prognosis-associated genes were identified, with TP53 showing the highest mutation frequency. High FADS2 expression was linked to poorer prognosis and higher immune cell infiltration. FADS2 knockdown significantly decreased glutathione (GSH) levels, SLC7A11, and GPX4 expression, increased malondialdehyde (MDA) levels, indicating the promotion of Ferroptosis. Functional tests revealed knockdown FADS2 repressed CRC cell proliferation, migration, and invasion. SLC7A11 or GPX4 overexpression partially rescued the effects of FADS2 knockdown. Additionally, FADS2 knockdown enhances the chemosensitivity of CRC cells to oxaliplatin.

Conclusion: FADS2 is essential for encouraging CRC cell proliferation and tumor growth by preventing Ferroptosis. Targeting FADS2 may enhance Ferroptosis and suppress CRC progression, offering a possible course of treatment for CRC patients. The knockdown of FADS2 enhances the chemosensitivity of CRC cells to oxaliplatin, providing valuable insights for future clinical applications.

Keywords

FADS2; Cell proliferation; Colorectal cancer; Ferroptosis; Prognosis.

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