Effect of SLC7A11 Gene on Progression of Hepatocellular Carcinoma by Regualating  Iron Death Pathway

Liuzheng LI; Leisheng XU; Kanghong LUO; Mingting ZHANG; Yan WANG; Xuechang GAO; Jiawei FENG; Guocha GONG

doi:10.12259/j.issn.2095-610X.S20251004

Volume 46 Issue 10

Oct. 2025

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Article Navigation > Journal of Kunming Medical University > 2025 > 46(10): 32-43

Liuzheng LI, Leisheng XU, Kanghong LUO, Mingting ZHANG, Yan WANG, Xuechang GAO, Jiawei FENG, Guocha GONG. Effect of SLC7A11 Gene on Progression of Hepatocellular Carcinoma by Regualating Iron Death Pathway[J]. Journal of Kunming Medical University, 2025, 46(10): 32-43. doi: 10.12259/j.issn.2095-610X.S20251004

Citation:

Liuzheng LI, Leisheng XU, Kanghong LUO, Mingting ZHANG, Yan WANG, Xuechang GAO, Jiawei FENG, Guocha GONG. Effect of SLC7A11 Gene on Progression of Hepatocellular Carcinoma by Regualating Iron Death Pathway[J]. Journal of Kunming Medical University, 2025, 46(10): 32-43. doi: 10.12259/j.issn.2095-610X.S20251004

Citation:

Liuzheng LI, Leisheng XU, Kanghong LUO, Mingting ZHANG, Yan WANG, Xuechang GAO, Jiawei FENG, Guocha GONG. Effect of SLC7A11 Gene on Progression of Hepatocellular Carcinoma by Regualating Iron Death Pathway[J]. Journal of Kunming Medical University, 2025, 46(10): 32-43. doi: 10.12259/j.issn.2095-610X.S20251004

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Effect of SLC7A11 Gene on Progression of Hepatocellular Carcinoma by Regualating Iron Death Pathway

doi: 10.12259/j.issn.2095-610X.S20251004

Department of Hepatobiliary Surgery，Lincang People’s Hospital，Lincang Yunnan 677000，China

Received Date: 2025-02-27
Publish Date: 2025-10-28

Abstract

Abstract

Objective To investigate the mechanism by which the SLC7A11 gene regulates the development and progression of hepatocellular carcinoma （HCCLM3） through the ferroptosis pathway, and to evaluate its potential as a therapeutic target. Methods Differentially expressed ferroptosis-related genes in liver cancer were screened based on data from the TCGA and ICGC databases. Detection of mRNA expression levels of TERT, MIOX, MYCN, NOX4, and SLC7A11 in tumor and adjacent non-tumorous tissues from 32 clinical liver cancer samples using qRT-PCR. Further analysis of SLC7A11 and its downstream molecules SLC3A2, GSS, and GPX4 was performed through qRT-PCR, Western blot, and IHC to assess expression levels and tissue distribution. A stable SLC7A11-knockdown HCCLM3 cell line was constructed and used to establish a subcutaneous xenograft tumor model in nude mice to evaluate its effect on tumor growth. Mice were divided into two groups （n = 6 per group）: HCCLM3 + sh-NC and HCCLM3 + sh-SLC7A11. Serum levels of IL-6, IL-1β, and TNF-α were measured using ELISA. Histopathological changes in tumor tissues were examined by H&E staining, and the expression of key genes was validated through multiple approaches. Results Bioinformatics analysis showed high expression of SLC7A11 in hepatocellular carcinoma tissues （P < 0.05）, significantly associated with poor patient prognosis. Clinical sample validation revealed significantly higher expression of SLC7A11, SLC3A2, GSS, and GPX4 in cancer tissues compared to control groups （All P < 0.05）. SLC7A11 knockdown significantly inhibited tumor volume and wet weight （P < 0.05）, and H&E staining showed reduced vascular density in the sh-SLC7A11 group. ELISA results showed elevated serum levels of IL-1β, IL-6, and TNF-α in the sh-SLC7A11 group. qRT-PCR, Western blot, and IHC all showed significantly downregulated expression of SLC7A11, SLC3A2, GSS, and GPX4 in tumor tissues （All P < 0.05）. Conclusion SLC7A11 inhibits ferroptosis by regulating the GSH-GPX4 axis, promoting hepatocellular carcinoma cell growth. Targeted inhibition of SLC7A11 can induce tumor cell ferroptosis and suppress tumor progression, suggesting it may be an important therapeutic target for hepatocellular carcinoma.
- SLC7A11,
- Gene,
- Ferroptosis,
- Hepatocellular carcinoma

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