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

Authors Xu P, Wu M, Chen H, Xu J, Wu M, Li M, Qian F, Xu J

Received 3 July 2015

Accepted for publication 22 September 2015

Published 8 January 2016 Volume 2016:9 Pages 191—202

DOI https://doi.org/10.2147/OTT.S91748

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Dekuang Zhao

Peer reviewer comments 4

Editor who approved publication: Dr Faris Farassati


Ping Xu,1,2 Meiying Wu,2,3 Hui Chen,1,2 Junchi Xu,1,2 Minjuan Wu,1 Ming Li,4 Feng Qian,4 Junhua Xu2,4

1Inspection Center, Affiliated Infectious Hospital of Soochow University, 2Key Laboratory of TB Prevention and Cure of Suzhou City, 3Department of Respiratory Medicine, Affiliated Infectious Hospital of Soochow University, 4Department of Infectious Diseases, Affiliated Infectious Hospital of Soochow University, Suzhou, Jiangsu Province, People’s Republic of China

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: soft cluster analysis, co-regulated genes, transcription factors, microRNAs, combined network

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