Hepatitis C Virus Protein Interaction Network Analysis Based on Hepatocellular Carcinoma.
Epidemiological studies have validated the association between hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). An increasing number of studies show that protein-protein interactions (PPIs) between HCV proteins and host proteins play a vital role in infection and mediate HCC progression. In this work, we collected all published interaction between HCV and human proteins, which include 455 unique human proteins participating in 524 HCV-human interactions. Then, we construct the HCV-human and HCV-HCC protein interaction networks, which display the biological knowledge regarding the mechanism of HCV pathogenesis, particularly with respect to pathogenesis of HCC. Through in-depth analysis of the HCV-HCC interaction network, we found that interactors are enriched in the JAK/STAT, p53, MAPK, TNF, Wnt, and cell cycle pathways. Using a random walk with restart algorithm, we predicted the importance of each protein in the HCV-HCC network and found that AKT1 may play a key role in the HCC progression. Moreover, we found that NS5A promotes HCC cells proliferation and metastasis by activating AKT/GSK3β/β-catenin pathway. This work provides a basis for a detailed map tracking new cellular interactions of HCV and identifying potential targets for HCV-related hepatocellular carcinoma treatment.
Xi'an Center for Disease Control and Prevention, Xi'an, China.
Yuewen
Y
Han
The General Hospital of Shenyang Military, Shenyang, China.
Jun
J
Niu
Air Force Aviation Medicine Identification and Training Center, Dalian, China.
Dong
D
Wang
Xi'an Center for Disease Control and Prevention, Xi'an, China.|Air Force Aviation Medicine Identification and Training Center, Dalian, China.
Yuanyuan
Y
Li
D000465:Algorithms; D006528:Carcinoma, Hepatocellular / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D000071679:Glycogen Synthase Kinase 3 beta / Q000378:metabolism; D016174:Hepacivirus / Q000378:metabolism* / Q000472:pathogenicity; D019698:Hepatitis C, Chronic / Q000150:complications / Q000378:metabolism; D006801:Humans; D008113:Liver Neoplasms / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D009363:Neoplasm Proteins / Q000378:metabolism*; D060066:Protein Interaction Maps; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D017361:Viral Nonstructural Proteins / Q000378:metabolism; D014764:Viral Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism; D012324:RNA-Dependent RNA Polymerase
D000071679:Glycogen Synthase Kinase 3 beta; D009363:Neoplasm Proteins; D051057:Proto-Oncogene Proteins c-akt; D017361:Viral Nonstructural Proteins; D014764:Viral Proteins; D051176:beta Catenin; C495270:CTNNB1 protein, human; C000605506:GSK3B protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase