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2018 ; 15
(5
): 6815-6824
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Identification and functional analysis of a core gene module associated with
hepatitis C virus-induced human hepatocellular carcinoma progression
#MMPMID29725417
Bai G
; Zheng W
; Ma W
Oncol Lett
2018[May]; 15
(5
): 6815-6824
PMID29725417
show ga
Hepatitis C virus (HCV)-induced human hepatocellular carcinoma (HCC) progression
may be due to a complex multi-step processes. The developmental mechanism of
these processes is worth investigating for the prevention, diagnosis and therapy
of HCC. The aim of the present study was to investigate the molecular mechanism
underlying the progression of HCV-induced hepatocarcinogenesis. First, the
dynamic gene module, consisting of key genes associated with progression between
the normal stage and HCC, was identified using the Weighted Gene Co-expression
Network Analysis tool from R language. By defining those genes in the module as
seeds, the change of co-expression in differentially expressed gene sets in two
consecutive stages of pathological progression was examined. Finally, interaction
pairs of HCV viral proteins and their directly targeted proteins in the
identified module were extracted from the literature and a comprehensive
interaction dataset from yeast two-hybrid experiments. By combining the
interactions between HCV and their targets, and protein-protein interactions in
the Search Tool for the Retrieval of Interacting Genes database (STRING), the
HCV-key genes interaction network was constructed and visualized using Cytoscape
software 3.2. As a result, a module containing 44 key genes was identified to be
associated with HCC progression, due to the dynamic features and functions of
those genes in the module. Several important differentially co-expressed gene
pairs were identified between non-HCC and HCC stages. In the key genes, cyclin
dependent kinase 1 (CDK1), NDC80, cyclin A2 (CCNA2) and rac GTPase activating
protein 1 (RACGAP1) were shown to be targeted by the HCV nonstructural proteins
NS5A, NS3 and NS5B, respectively. The four genes perform an intermediary role
between the HCV viral proteins and the dysfunctional module in the HCV key genes
interaction network. These findings provided valuable information for
understanding the mechanism of HCV-induced HCC progression and for seeking drug
targets for the therapy and prevention of HCC.