Ke Jiang, Botian Huang, Shasha He, Meiyan Zhu, Xiao Zhao, Miaowen Liu, Zhenwei Peng, Yan Wang, Yong Chen
{"title":"SOX4介导肝癌中癌相关成纤维细胞相关放射耐药","authors":"Ke Jiang, Botian Huang, Shasha He, Meiyan Zhu, Xiao Zhao, Miaowen Liu, Zhenwei Peng, Yan Wang, Yong Chen","doi":"10.1007/s13402-025-01088-z","DOIUrl":null,"url":null,"abstract":"<p><strong>Purpose: </strong>Cancer-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).</p><p><strong>Methods: </strong>CAFs 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.</p><p><strong>Results: </strong>Our 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.</p><p><strong>Conclusion: </strong>CAFs 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.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>","PeriodicalId":9690,"journal":{"name":"Cellular Oncology","volume":" ","pages":""},"PeriodicalIF":4.8000,"publicationDate":"2025-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"SOX4 mediates cancer-associated fibroblasts related radioresistance in hepatocellular carcinoma.\",\"authors\":\"Ke Jiang, Botian Huang, Shasha He, Meiyan Zhu, Xiao Zhao, Miaowen Liu, Zhenwei Peng, Yan Wang, Yong Chen\",\"doi\":\"10.1007/s13402-025-01088-z\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Purpose: </strong>Cancer-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).</p><p><strong>Methods: </strong>CAFs 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.</p><p><strong>Results: </strong>Our 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.</p><p><strong>Conclusion: </strong>CAFs 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.</p><p><strong>Clinical trial number: </strong>Not applicable.</p>\",\"PeriodicalId\":9690,\"journal\":{\"name\":\"Cellular Oncology\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":4.8000,\"publicationDate\":\"2025-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Cellular Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s13402-025-01088-z\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"Medicine\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Cellular Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s13402-025-01088-z","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"Medicine","Score":null,"Total":0}
SOX4 mediates cancer-associated fibroblasts related radioresistance in hepatocellular carcinoma.
Purpose: Cancer-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).
Methods: CAFs 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.
Results: Our 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.
Conclusion: CAFs 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.
Cellular OncologyBiochemistry, Genetics and Molecular Biology-Cancer Research
CiteScore
10.40
自引率
1.50%
发文量
0
审稿时长
16 weeks
期刊介绍：
The Official Journal of the International Society for Cellular Oncology
Focuses on translational research
Addresses the conversion of cell biology to clinical applications
Cellular Oncology publishes scientific contributions from various biomedical and clinical disciplines involved in basic and translational cancer research on the cell and tissue level, technical and bioinformatics developments in this area, and clinical applications. This includes a variety of fields like genome technology, micro-arrays and other high-throughput techniques, genomic instability, SNP, DNA methylation, signaling pathways, DNA organization, (sub)microscopic imaging, proteomics, bioinformatics, functional effects of genomics, drug design and development, molecular diagnostics and targeted cancer therapies, genotype-phenotype interactions.
A major goal is to translate the latest developments in these fields from the research laboratory into routine patient management. To this end Cellular Oncology forms a platform of scientific information exchange between molecular biologists and geneticists, technical developers, pathologists, (medical) oncologists and other clinicians involved in the management of cancer patients.
In vitro studies are preferentially supported by validations in tumor tissue with clinicopathological associations.
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