title: NS5ATP9 contributes to inhibition of cell proliferation by hepatitis C virus (HCV) nonstructural protein 5A (NS5A) via MEK/extracellular signal regulated kinase (ERK) pathway.
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.
authors.affiliation: Institute of Infectious Diseases, Beijing Ditan Hospital, Capital Medical University, Beijing 100015, China. jun.cheng.ditan@gmail.com.
authors.forename: Qi
authors.initials: Q
authors.lastname: Wang
authors.forename: Yongsheng
authors.initials: Y
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Li
authors.forename: Xuesong
authors.initials: X
authors.lastname: Gao
authors.forename: Shunai
authors.initials: S
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Cheng
mesh_terms: D015153:Blotting, Western; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D056945:Hep G2 Cells; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000378:metabolism*; D020935:MAP Kinase Signaling System; D010766:Phosphorylation; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017361:Viral Nonstructural Proteins / Q000235:genetics / Q000378:metabolism*; D012324:RNA-Dependent RNA Polymerase
chemical_list: D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D048049:Extracellular Signal-Regulated MAP Kinases; D048369:MAP Kinase Kinase 1; D017361:Viral Nonstructural Proteins; C425208:PCLAF protein, human; C087036:NS-5 protein, hepatitis C virus; D012324:RNA-Dependent RNA Polymerase