NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development

Chen，Wenbiao1; Guo，Liliangzi1; Xu，Huixuan2; Dai，Yong2; Yao，Jun1; Wang，Lisheng1

2024-12-01

10.1038/s41389-024-00515-4

Oncogenesis   影响因子和分区

2157-9024

Our study aimed to elucidate the molecular mechanisms underlying NAC1 (nucleus accumbens associated 1) transcriptional regulation of LDHA and its role in HBV immune evasion, thus contributing to the development of cirrhosis and hepatocellular carcinoma (HCC). Utilizing public datasets, we performed differential gene expression and weighted gene co-expression network analysis (WGCNA) on HBV-induced cirrhosis/HCC data. We identified candidate genes by intersecting differentially expressed genes with co-expression modules. We validated these genes using the TCGA database, conducting survival analysis to pinpoint key genes affecting HBV-HCC prognosis. We also employed the TIMER database for immune cell infiltration data and analyzed correlations with identified key genes to uncover potential immune escape pathways. In vitro, we investigated the impact of NAC1 and LDHA on immune cell apoptosis and HBV immune evasion. In vivo, we confirmed these findings using an HBV-induced cirrhosis model. Bioinformatics analysis revealed 676 genes influenced by HBV infection, with 475 genes showing differential expression in HBV-HCC. NAC1 emerged as a key gene, potentially mediating HBV immune escape through LDHA transcriptional regulation. Experimental data demonstrated that NAC1 transcriptionally activates LDHA, promoting immune cell apoptosis and HBV immune evasion. Animal studies confirmed these findings, linking NAC1-mediated LDHA activation to cirrhosis and HCC development. NAC1, highly expressed in HBV-infected liver cells, likely drives HBV immune escape by activating LDHA expression, inhibiting CD8 + T cells, and promoting cirrhosis and HCC development.

SCI

英语

第一 ; 通讯

2-s2.0-85192009406

Scopus

1.Department of Gastroenterology,Shenzhen People’s Hospital,The Second Clinical Medical College,Jinan University; The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,518020,China
2.Clinical Medical Research Center,Guangdong Provincial Engineering Research Center of Autoimmune Disease Precision Medicine,Shenzhen People’s Hospital,The Second Clinical Medical College,Jinan University; The First Affiliated Hospital,Southern University of Science and Technology,Shenzhen,518020,China

Chen，Wenbiao,Guo，Liliangzi,Xu，Huixuan,et al. NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development[J]. Oncogenesis,2024,13(1).

Chen，Wenbiao,Guo，Liliangzi,Xu，Huixuan,Dai，Yong,Yao，Jun,&Wang，Lisheng.(2024).NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development.Oncogenesis,13(1).

Chen，Wenbiao,et al."NAC1 transcriptional activation of LDHA induces hepatitis B virus immune evasion leading to cirrhosis and hepatocellular carcinoma development".Oncogenesis 13.1(2024).