Bioinformatics analysis of hepatitis C virus genotype 2a-induced human hepatocellular carcinoma in Huh7 cells

Abstract

Hepatocellular carcinoma (HCC) is a liver cancer that could be induced by hepatitis C virus genotype 2a Japanese fulminant hepatitis-1 (JFH-1) strain. The aim of this study was to investigate the molecular mechanisms of HCC. The microarray data GSE20948 includes 14 JFH-1- and 14 mock (equal volume of medium [control])-infected Huh7 samples. The data were downloaded from the Gene Expression Omnibus. After data processing, soft cluster analyses were performed to identify co-regulated genes with similar temporal expression patterns. Functional and pathway enrichment analyses, as well as functional annotation analysis, were performed. Subsequently, combined networks of protein-protein interaction network, microRNA regulatory network, and transcriptional regulatory network were constructed. Hub nodes, modules, and five clusters of co-regulated genes were also identified. In total, 173 up and 207 down co-regulated genes were separately identified in JFH-1-infected Huh7 cells compared with those of control cells. Functional enrichment analysis indicated that up co-regulated genes were related to skeletal system morphogenesis and neuron differentiation and down co-regulated genes were related to steroid/cholesterol/sterol metabolisms. Hub genes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) were identified. Transcription factors IRF1 and Foxa1 were the targets of miR-130a, miR-17-5p, and miR-20a. PPARGC1A was targeted by miR-29 family, and MSMO1 was the target of miR-23 family. Hub nodes (such as IRF1, GBP1, ICAM1, Foxa1, DHCR7, HMGCS2, and MSMO1) and microRNAs might be used as candidate biomarkers of JFH-1-infected HCC.

Keywords: co-regulated genes; combined network; microRNAs; soft cluster analysis; transcription factors.

Figure 1

Soft cluster analysis of the temporal expression profiles of co-regulated genes. Note: Membership values were color encoded with red denoting high membership values and green denoting low membership values.

Figure 2

The combination of the protein-to-protein interaction network, miRNA regulatory network, and transcriptional regulatory network of the up co-regulated (A) and down co-regulated genes (B). Notes: Gene, miRNA, and TF are represented by nodes. Circles indicate genes, triangles indicate transcription factors, and quadrangles indicate miRNA. Lines between nodes indicate the interrelationships. Abbreviations: miRNA, microRNA; TF, transcription factor.

Figure 3

The most significant modules of the networks of the up co-regulated (A) and down co-regulated genes (B). Notes: Genes are represented by nodes. Circles indicate genes, triangles indicate transcription factors, and quadrangles indicate miRNAs. Lines between nodes indicate the interrelationships.

Figure 4

Network of the most hub nodes in the combined network of up co-regulated (A) and down co-regulated genes (B). Notes: Gene and TF are represented by nodes. Circles indicate genes and triangles indicate transcription factors. Lines between nodes indicate the interrelationships. Abbreviation: TF, transcription factor.