Clonorchis sinensis infection remodels chromatin accessibility in hepatocellular carcinoma

作者：Weilong Yang, Caibiao Wei, Junxian Chen, Qiumei Lin, Yuling Qin, Taijun Huang, Xueling Deng, Mulin Jun Li, Zeli Tang, Min Fang · 发表于：Parasites & Vectors · 年份：2025 · DOI：10.1186/s13071-025-06909-6 · 被引用次数：2 · 研究领域：Parasites and Host Interactions、Protease and Inhibitor Mechanisms、Helminth infection and control

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 ( Cs ESPs) 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 metab...