Computational networks of activating transcription factor 3 gene in Huh7 cell lines and hepatitis C virus-infected Huh7 cell lines.

Activating transcription factor 3 (ATF3) is an adaptive-response gene of the ATF family. ATF3 activity may be induced in response to a number of different stress-associated signals and ATF3 is involved in a variety of cellular processes. However, the functions of ATF3 and its molecular networks in human hepatoma cells lines and hepatitis C virus-infected Huh7 (HCV-Huh7) cells are not well understood. In the present study, ATF3 regulatory networks in Huh7 and HCV-Huh7 cell lines were established using the linear programming-based GRNinfer software and molecule annotation system 3.0 software. The gene expression omnibus dataset, GSE20948, was analyzed. The resulting network consisted of clusters located upstream and downstream of ATF3 in Huh7 and HCV-Huh7 cell lines. Using the annotation, visualization and integrated discovery (DAVID) software, 10 activation and 2 inhibition enriched functional annotation clusters were identified downstream of ATF3 in HCV-Huh7 cells. However, there were no enriched functional annotation clusters identified upstream of ATF3 in HCV-Huh7 cells. Furthermore, no clusters were identified downstream nor upstream of ATF3 in Huh7 cells. Gene ontology term and Kyoto encyclopedia of genes and genomes pathway analyses demonstrated that ATF3 may be involved in a number of biological processes, in particular, in metabolism regulation in HCV-Huh7 cells. It is hypothesized that the ATF3 pathway may be activated in Huh7 cells following HCV infection and that it is a potential hub' in the network of HCV-Huh7 cells.