Hepatitis C virus stimulates the expression of cyclooxygenase-2 via oxidative stress: role of prostaglandin E2 in RNA replication
Authors: Aleem Siddiqui
Gulam Waris
Journal: Journal of Virology (2005)
Discipline: MICROBIOLOGY
Keywords: Hepatitis C virus; HCV; chronic liver disease; liver cirrhosis; hepatocellular carcinoma
Affiliations: Department of Microbiology, University of Colorado Health Sciences Center, 80262, USA., Department of Microbiology and Program in Molecular Biology, University of Colorado Health Sciences Center, 4200 E. 9th Ave., Denver, Colorado 80262

Abstract:  Hepatitis C virus (HCV) infection is a major cause of chronic liver disease, which can lead to the development of liver cirrhosis and hepatocellular carcinoma. Recently, the activation of cyclooxygenase-2 (Cox-2) has been implicated in the HCV-associated hepatocellular carcinoma. In this study, we focus on the signaling pathway leading to Cox-2 activation induced by HCV gene expression. Here, we demonstrate that the HCV-induced reactive oxygen species and subsequent activation of NF-kappaB mediate the activation of Cox-2. The HCV-induced Cox-2 was sensitive to antioxidant (pyrrolidine dithiocarbamate), Ca(2+) chelator (BAPTA-AM), and calpain inhibitor (N-acetyl-Leu-Leu-Met-H). The levels of prostaglandin E(2) (PGE(2)), the product of Cox-2 activity, are increased in HCV-expressing cells. Furthermore, HCV-expressing cells treated with the inhibitors of Cox-2 (celecoxib and NS-398) showed significant reduction in PGE(2) levels. We also observed the enhanced phosphorylation of Akt and its downstream substrates glycogen synthase kinase-3beta and proapoptotic Bad in the HCV replicon-expressing cells. These phosphorylation events were sensitive to inhibitors of Cox-2 (celecoxib and NS-398) and phosphatidylinositol 3-kinase (LY294002). Our results also suggest a potential role of Cox-2 and PGE(2) in HCV RNA replication. These studies provide insight into the mechanisms by which HCV induces intracellular events relevant to liver pathogenesis associated with viral infection. 

Retracted: Yes

PubPeer comments:
 Figure 2C. The  blank and  negative photos appear to show an overlap. Shown with blue boxes. Could the authors please check? ![file] , 
 Figure 7D. Two panels appear to show an area of overlap, if one of the two photos is mirrored. Shown with red boxes. ![file] , 
 Corrigendum published, [22 January 2020] . -------------------------------------- The authors regret that in previous version of manuscript, we accidently presented the wrong images in Fig. 2C and 7D. The corrected version of Fig. 2C and 7D have been provided below. This correction does not impact the results and conclusions of this article. ![] ![] The authors would like to apologize for any inconvenience caused. , 
 I am surprised that Cancer Letters accepts a correction of obvious falsification of data. Interestingly, much of the data presented in this article have been reused in another publication (Tian, K et al., 2015; Cancer Gene Therapy) which has been retracted, including Figure 1b, 2c, 5d,e and 7b,d. , 
 #4 The retraction note for [Tian et at (2015)] is extensive, and connects that paper to four others (including the present paper). ,