The NuRD (Nucleosome Remodeling and Deacetylation) complex is a repressive complex in gene transcription by modulating chromatin accessibility of target genes to transcription factors and RNA polymerase II. Although individual subunits of the complex have been implicated in many other cancer types, the complex’s role in human hepatocellular carcinoma (HCC) is not fully understood. More importantly, the NuRD complex has not yet been investigated as a whole in cancers. We analyzed the expression of the NuRD complex in HCC and evaluated the prognostic value of NuRD complex expression in HCC using the RNA-seq data obtained from the TCGA project. We examined the effect of CHD4 knockdown on HCC cell proliferation, apoptosis, migration, invasion, epithelial-mesenchymal transition, colony-forming ability, and on complement gene expression. We also performed bioinformatic analyses to investigate the correlation between the NuRD complex expression and immune infiltration. We found that nine subunits, out of 14 subunits of the NuRD complex examined, were significantly overexpressed in HCC, and their expression levels were positively correlated with cancer progression. More importantly, our data also demonstrated that these subunits tended to be overexpressed as a whole in HCC. Subsequent studies demonstrated that knockdown of CHD4 in HCC cells inhibits cell proliferation, migration, invasion, and colony-forming ability and promotes apoptosis of HCC cells, indicating that the CHD4/NuRD complex plays oncogenic roles in HCC. Further analysis revealed that the CHD4/NuRD complex regulates complement gene expression in HCC. Intriguingly, we found that the CHD4/NuRD complex expression was inversely correlated with CD8 T cell infiltration in HCC. Our data demonstrate that the CHD4/NuRD complex plays an oncogenic role in human HCC and regulates complement gene expression in HCC cells. The results of inverse correlation between the CHD4/NuRD complex and CD8 T cell and DC cell infiltration in HCC suggest that the CHD4/NuRD complex not only plays direct regulatory roles in HCC cells, but also has an impact on the immune microenvironment of HCC.

中文翻译：

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CHD4 / NuRD复合物调节补体基因表达，并与人肝细胞癌中CD8 T细胞浸润相关。

NuRD（核小体重塑和去乙酰化）复合物是一种通过调控靶基因对转录因子和RNA聚合酶II的染色质可及性而在基因转录中的抑制性复合物。尽管复合物的各个亚基已涉及许多其他类型的癌症，但该复合物在人肝细胞癌（HCC）中的作用尚不完全清楚。更重要的是，尚未对NuRD复合物整体进行癌症研究。我们使用TCGA项目获得的RNA-seq数据分析了NuCC复合物在肝癌中的表达，并评估了NuRD复合物在肝癌中的预后价值。我们检查了CHD4基因敲低对HCC细胞增殖，凋亡，迁移，侵袭，上皮-间质转化，集落形成能力以及补体基因表达的影响。我们还进行了生物信息学分析，以研究NuRD复合物表达与免疫浸润之间的相关性。我们发现在所检查的NuRD复合物的14个亚基中有9个亚基在肝癌中显着过表达，并且它们的表达水平与癌症进展呈正相关。更重要的是，我们的数据还表明，这些亚基在HCC中总体上倾向于过表达。随后的研究表明，敲除HCC细胞中的CHD4会抑制细胞增殖，迁移，侵袭和集落形成能力，并促进HCC细胞凋亡，这表明CHD4 / NuRD复合物在HCC中起致癌作用。进一步的分析表明，CHD4 / NuRD复合物调节肝癌中补体基因的表达。有趣的是 我们发现CHD4 / NuRD复合物表达与肝癌中CD8 T细胞浸润呈负相关。我们的数据表明，CHD4 / NuRD复合物在人类HCC中起着致癌作用，并调节HCC细胞中的补体基因表达。CHD4 / NuRD复合物与CD8 T细胞和DC细胞在HCC中的浸润呈负相关，表明CHD4 / NuRD复合物不仅在HCC细胞中发挥直接调节作用，而且对HCC的免疫微环境有影响。