Park In-Woo, Fiadjoe Hope K, Hoteit Tamara, Chaudhary Pankaj
Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, Fort Worth, Texas, 76107, USA.
Department of Microbiology, Immunology, and Genetics, University of North Texas Health Science Center, Fort Worth, Texas, 76107, USA.
Virus Res. 2025 Jul;357:199593. doi: 10.1016/j.virusres.2025.199593. Epub 2025 Jun 7.
Our previous transcriptome analysis revealed that hepatitis C virus (HCV) infection in hepatocytes regulates the expression of numerous hepatocellular genes in a liver disease stage-specific manner. Based on the fold changes at different stages and the known relevant function of the cellular genes with respect to hepatocellular carcinoma (HCC) and through comprehensive examination with various in silico assays, such as heatmap and volcano analysis for the differential expression, the Cancer Genome Atlas - Hepatocellular Carcinoma (TCGA-HCC) analysis, and molecular approaches, such as qRT-PCR, immunoblot analyses, we have chosen the two up-regulated genes - aldo-keto reductase family 1 member B10 (AKR1B10) and hexokinase domain containing 1 (HKDC1), and two down-regulated genes - glycine N-methyltransferase (GNMT) and C-type lectin domain family 4, member M (CLEC4M), and validated their differential expressions of the genes at disparate stages of liver disease with respect to the development of potential therapeutic targets against HCV-mediated hepatocellular carcinoma (HCC). These data suggested that the differentially expressed genes at various stages could serve as prognostic and diagnostic markers for liver disease progression and may also be utilized in developing therapeutic drugs.
我们之前的转录组分析表明，肝细胞中的丙型肝炎病毒（HCV）感染以肝脏疾病阶段特异性的方式调节众多肝细胞基因的表达。基于不同阶段的倍数变化以及细胞基因与肝细胞癌（HCC）相关的已知功能，并通过各种计算机分析方法（如差异表达的热图和火山分析）、癌症基因组图谱 - 肝细胞癌（TCGA-HCC）分析以及分子方法（如qRT-PCR、免疫印迹分析）进行综合检查，我们选择了两个上调基因——醛糖酮还原酶家族1成员B10（AKRIB10）和含己糖激酶结构域1（HKDC1），以及两个下调基因——甘氨酸N-甲基转移酶（GNMT）和C型凝集素结构域家族4成员M（CLEC4M），并验证了它们在肝脏疾病不同阶段相对于针对HCV介导的肝细胞癌（HCC）开发潜在治疗靶点的基因差异表达。这些数据表明，不同阶段差异表达的基因可作为肝脏疾病进展的预后和诊断标志物，也可用于开发治疗药物。
