Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma
Abstract Background Hepatocellular carcinoma (HCC) is a major global health concern, accounting for a significant proportion of liver cancer cases and related deaths. Clonorchis sinensis (C. sinensis) infection, a recognized carcinogen, has been implicated in the progression of liver diseases, inclu...
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| Format: | Article |
| Language: | English |
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BMC
2025-07-01
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| Series: | Parasites & Vectors |
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| Online Access: | https://doi.org/10.1186/s13071-025-06909-6 |
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| author | Weilong Yang Caibiao Wei Junxian Chen Qiumei Lin Yuling Qin Taijun Huang Xueling Deng Mulin Jun Li Zeli Tang Min Fang |
| author_facet | Weilong Yang Caibiao Wei Junxian Chen Qiumei Lin Yuling Qin Taijun Huang Xueling Deng Mulin Jun Li Zeli Tang Min Fang |
| author_sort | Weilong Yang |
| collection | DOAJ |
| description | Abstract Background Hepatocellular carcinoma (HCC) is a major global health concern, accounting for a significant proportion of liver cancer cases and related deaths. Clonorchis sinensis (C. sinensis) infection, a recognized carcinogen, has been implicated in the progression of liver diseases, including HCC. However, the precise epigenetic mechanisms underlying C. sinensis-associated HCC remain to be elucidated. Methods To investigate the role of chromatin accessibility in C. sinensis-related HCC progression, we performed an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) analyses of C. sinensis-infected (C. sinensis +) and non-C. sinensis-infected (C. sinensis −) HCC tumors. Integrated analyses were conducted to assess chromatin accessibility, transcription factor (TF) motifs, and histone modifications using ATAC-seq, RNA-seq, and classical chromatin immunoprecipitation-sequencing (ChIP-seq) datasets. A scratch wound assay was used to evaluate the effects of C. sinensis excretory/secretory products (CsESPs) on HCC cell migration. Results ATAC-seq analysis revealed 9,396 differentially accessible regions (DARs) in C. sinensis + HCC tumors compared with C. sinensis − HCC tumors. Additionally, several crucial TFs enriched in DARs were identified, including HNF4A, FOXO1, ELF4, and RELA. Combined ATAC-seq and RNA-seq analyses further revealed differentially expressed genes (DEGs) associated with metabolism, immune regulation, and cytoskeletal dynamics. Chromatin accessibility was closely associated with histone modifications such as H3K9ac, H3K4me2, H3K4me3, H3K27ac, H3K4me1, and CTCF binding. Notably, C. sinensis infection significantly increased the migratory capacity of HCC cells, as confirmed by molecular assays and clinical observations. Conclusions Our study demonstrates that C. sinensis infection remodels chromatin accessibility and may contribute to HCC progression. Our work offers valuable insights into the pathogenesis of HCC in the context of parasitic infection and lays the groundwork for future biomarker and therapeutic target discovery. Graphical abstract |
| format | Article |
| id | doaj-art-96aef1e99db94eec86cfbba7f21189a3 |
| institution | Kabale University |
| issn | 1756-3305 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Parasites & Vectors |
| spelling | doaj-art-96aef1e99db94eec86cfbba7f21189a32025-08-20T03:45:48ZengBMCParasites & Vectors1756-33052025-07-0118111610.1186/s13071-025-06909-6Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinomaWeilong Yang0Caibiao Wei1Junxian Chen2Qiumei Lin3Yuling Qin4Taijun Huang5Xueling Deng6Mulin Jun Li7Zeli Tang8Min Fang9Guangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Clinical Laboratory, Guangxi Medical University Cancer HospitalDepartment of Clinical Laboratory, Guangxi Medical University Cancer HospitalDepartment of Clinical Laboratory, Guangxi Medical University Cancer HospitalDepartment of Clinical Laboratory, Guangxi Medical University Cancer HospitalDepartment of Clinical Laboratory, Guangxi Medical University Cancer HospitalDepartment of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical UniversityGuangzhou Women and Children’s Medical Center, Guangzhou Medical UniversityDepartment of Cell Biology and Genetics, School of Basic Medical Sciences, Guangxi Medical UniversityDepartment of Clinical Laboratory, Guangxi Medical University Cancer HospitalAbstract Background Hepatocellular carcinoma (HCC) is a major global health concern, accounting for a significant proportion of liver cancer cases and related deaths. Clonorchis sinensis (C. sinensis) infection, a recognized carcinogen, has been implicated in the progression of liver diseases, including HCC. However, the precise epigenetic mechanisms underlying C. sinensis-associated HCC remain to be elucidated. Methods To investigate the role of chromatin accessibility in C. sinensis-related HCC progression, we performed an assay for transposase-accessible chromatin with high-throughput sequencing (ATAC-seq) and RNA sequencing (RNA-seq) analyses of C. sinensis-infected (C. sinensis +) and non-C. sinensis-infected (C. sinensis −) HCC tumors. Integrated analyses were conducted to assess chromatin accessibility, transcription factor (TF) motifs, and histone modifications using ATAC-seq, RNA-seq, and classical chromatin immunoprecipitation-sequencing (ChIP-seq) datasets. A scratch wound assay was used to evaluate the effects of C. sinensis excretory/secretory products (CsESPs) on HCC cell migration. Results ATAC-seq analysis revealed 9,396 differentially accessible regions (DARs) in C. sinensis + HCC tumors compared with C. sinensis − HCC tumors. Additionally, several crucial TFs enriched in DARs were identified, including HNF4A, FOXO1, ELF4, and RELA. Combined ATAC-seq and RNA-seq analyses further revealed differentially expressed genes (DEGs) associated with metabolism, immune regulation, and cytoskeletal dynamics. Chromatin accessibility was closely associated with histone modifications such as H3K9ac, H3K4me2, H3K4me3, H3K27ac, H3K4me1, and CTCF binding. Notably, C. sinensis infection significantly increased the migratory capacity of HCC cells, as confirmed by molecular assays and clinical observations. Conclusions Our study demonstrates that C. sinensis infection remodels chromatin accessibility and may contribute to HCC progression. Our work offers valuable insights into the pathogenesis of HCC in the context of parasitic infection and lays the groundwork for future biomarker and therapeutic target discovery. Graphical abstracthttps://doi.org/10.1186/s13071-025-06909-6Clonorchis sinensisHepatocellular carcinomaChromatin accessibilityTranscription factorTumor progression |
| spellingShingle | Weilong Yang Caibiao Wei Junxian Chen Qiumei Lin Yuling Qin Taijun Huang Xueling Deng Mulin Jun Li Zeli Tang Min Fang Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma Parasites & Vectors Clonorchis sinensis Hepatocellular carcinoma Chromatin accessibility Transcription factor Tumor progression |
| title | Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma |
| title_full | Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma |
| title_fullStr | Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma |
| title_full_unstemmed | Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma |
| title_short | Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma |
| title_sort | clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma |
| topic | Clonorchis sinensis Hepatocellular carcinoma Chromatin accessibility Transcription factor Tumor progression |
| url | https://doi.org/10.1186/s13071-025-06909-6 |
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