ArticleCellular oncology (Dordrecht, Netherlands)2025
SOX4 mediates cancer-associated fibroblasts related radioresistance in hepatocellular carcinoma.
Article in Cellular oncology (Dordrecht, Netherlands), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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Who cites it
3 citing papers in PubMed.
- Radiation-Induced Alterations in Cancer-Associated Fibroblasts: Drivers of Tumor Radioresistance and Therapeutic Targets.Biomolecules · 2026Review
- PPIL1 promotes hepatocellular carcinoma progression and associates with poor prognosis.Naunyn-Schmiedeberg's archives of pharmacology · 2026Article
- Let-7a and miR-34a Interplay Potent Suppressive Roles in Hepatocellular Carcinoma via Co-TargetingInternational journal of molecular sciences · 2026Article
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9 authors.
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Abstract
purposeCancer-associated fibroblasts (CAFs), a crucial component of tumor microenvironment, play a critical role in tumorigenesis, progression, and conferring resistance to radiotherapy and chemotherapy. This study aimed to investigate the association between CAFs, CAF- related genes, and radioresistance in hepatocellular carcinoma (HCC).
methodsCAFs were isolated from HCC tissues and subsequently utilized for co-culturing with HCC cells using CAFs-conditioned medium. An orthotopic HCC mouse model was established by co-implanting CAFs and HCC cells. Through integrative analysis of three RNA-sequencing datasets (TCGA-LIHC tumor vs. normal tissues, Huh7 radioresistant vs. parent cells, and CAF vs. control group), CAF-associated prognostic genes were identified using comprehensive bioinformatics approaches. Experimental validation was performed by real-time quantitative PCR, western blot, immunohistochemistry, cell viability assays, and colony formation assays.
resultsOur findings demonstrated that CAFs significantly enhance radioresistance in HCC. Based on 13 CAF-related prognostic genes, TCGA-LIHC patients were stratified into two distinct clusters via consensus clustering, exhibiting significant differences in overall survival, immune cell infiltration, and therapeutic response. A prognostic nomogram incorporating three hub genes and clinical characteristics was developed. Notably, SOX4 was upregulated in tumor tissues, radioresistant cells, and CAF-exposed HCC cells, correlating with poor prognosis. SOX4 knockdown suppressed HCC proliferation and reversed CAF-induced radioresistance. Additionally, a competitive endogenous RNA (ceRNA) network of LINC00665/miR-122-5p/SOX4 was constructed.
conclusionCAFs serve as crucial mediators of radioresistance in HCC, and CAF-related genes provide valuable prognostic and therapeutic insights. SOX4 emerges as a promising therapeutic target to improve radiotherapy efficacy in HCC. CLINICAL TRIAL NUMBER: Not applicable.
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