Yang Weilong, Wei Caibiao, Chen Junxian, Lin Qiumei, Qin Yuling, Huang Taijun, Deng Xueling, Li Mulin Jun, Tang Zeli, Fang Min
Guangzhou Women and Children's Medical Center, Guangzhou Medical University, Guangzhou, China.
Department of Clinical Laboratory, Guangxi Medical University Cancer Hospital, Nanning, 530021, Guangxi, China.
Parasit Vectors. 2025 Jul 10;18(1):276. doi: 10.1186/s13071-025-06909-6.
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.
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.
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.
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.
肝细胞癌（HCC）是全球主要的健康问题，在肝癌病例及相关死亡中占很大比例。华支睾吸虫（C. sinensis）感染是一种公认的致癌物，与包括HCC在内的肝脏疾病进展有关。然而，华支睾吸虫相关HCC潜在的精确表观遗传机制仍有待阐明。
为研究染色质可及性在华支睾吸虫相关HCC进展中的作用，我们对感染华支睾吸虫（C. sinensis）和未感染华支睾吸虫（C. sinensis）的HCC肿瘤进行了转座酶可及染色质高通量测序（ATAC-seq）分析和RNA测序（RNA-seq）分析。利用ATAC-seq、RNA-seq和经典的染色质免疫沉淀测序（ChIP-seq）数据集进行综合分析，以评估染色质可及性、转录因子（TF）基序和组蛋白修饰。采用划痕实验评估华支睾吸虫排泄/分泌产物（CsESPs）对HCC细胞迁移的影响。
与未感染华支睾吸虫的HCC肿瘤相比，ATAC-seq分析在感染华支睾吸虫的HCC肿瘤中发现了9396个差异可及区域（DARs）。此外，还鉴定了几个在DARs中富集的关键TF，包括HNF4A、FOXO1、ELF4和RELA。联合ATAC-seq和RNA-seq分析进一步揭示了与代谢、免疫调节和细胞骨架动力学相关的差异表达基因（DEGs）。染色质可及性与组蛋白修饰如H3K9ac、H3K4me2、H3K4me3、H3K27ac、H3K4me1和CTCF结合密切相关。值得注意的是，分子检测和临床观察证实，华支睾吸虫感染显著增加了HCC细胞的迁移能力。
我们的研究表明，华支睾吸虫感染重塑了染色质可及性，并可能促进HCC进展。我们的工作为寄生虫感染背景下HCC的发病机制提供了有价值的见解，并为未来生物标志物和治疗靶点的发现奠定了基础。
