Abstract
Hepatitis C virus (HCV) nonstructural protein 5A (NS5A) is a remarkable protein as it clearly plays multiple roles in mediating viral replication, host-cell interactions and viral pathogenesis. However, on the impact of cell growth, there have been different study results. NS5ATP9, also known as KIAA0101, p15PAF, L5, and OEACT-1, was first identified as a proliferating cell nuclear antigen-binding protein. Earlier studies have shown that NS5ATP9 might play an important role in HCV infection. The aim of this study is to investigate the function of NS5ATP9 on hepatocellular carcinoma (HCC) cell lines proliferation under HCV NS5A expression. The results showed that overexpression of NS5ATP9 inhibited the proliferation of Bel7402 cells, whereas knockdown of NS5ATP9 by interfering RNA promoted the growth of HepG2 cells. Under HCV NS5A expression, RNA interference (RNAi) targeting of NS5ATP9 could reverse the inhibition of HepG2 cell proliferation, suggesting that NS5ATP9 might be an anti-proliferation gene that plays an important role in the suppression of cell growth mediated by HCV NS5A via MEK/ERK signaling pathway. These findings might provide new insights into HCV NS5A and NS5ATP9.
Highlights
Hepatitis C virus (HCV) is one of the most common pathogens of chronic hepatitis
nonstructural protein 5A (NS5A) expression, interfering RNA targeting of NS5ATP9 could reverse the inhibition of HepG2 cell proliferation, suggesting that NS5ATP9 could be an anti-proliferation gene that plays an important role in the suppression of cell growth mediated by HCV NS5A via Mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) signaling pathway
We found that NS5ATP9 knockdown could reverse the inhibition of HepG2 cell proliferation caused by HCV NS5A expression, clearly indicating the role of NS5ATP9 in the suppression of cell growth mediated by HCV NS5A
Summary
Hepatitis C virus (HCV) is one of the most common pathogens of chronic hepatitis. Persistent HCV infection often leads to liver cirrhosis and is associated with the development of hepatocellular carcinoma (HCC) [1,2]. There were studies that suggested NS5ATP9 is involved in the regulation of diverse processes such as DNA repair, apoptosis, cellular signaling pathway, cell cycle and cell growth [14,16,17,22,23,24,25,26]. NS5A expression, interfering RNA targeting of NS5ATP9 could reverse the inhibition of HepG2 cell proliferation, suggesting that NS5ATP9 could be an anti-proliferation gene that plays an important role in the suppression of cell growth mediated by HCV NS5A via MEK/ERK signaling pathway. This finding might provide new insights into the roles of HCV NS5A and NS5ATP9
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