Retraction Note:Dickkopf-1 contributes to hepatocellular carcinoma tumorigenesis by activating the Wnt/β-catenin signaling pathway

Retraction to:Signal Transduction and Targeted Therapy https://doi.org/10.1038/s41392-019-0082-5,published online 06 December 2019 The authors have retracted this article.After publication,concerns were raised regarding suspected overlap in the cell images in Figs.2 and 3.Specifically.

Inducible Rubicon facilitates viral replication by antagonizing interferon production

The RUN domain Beclin-1-interacting cysteine-rich-containing(Rubicon)protein is involved in the maturation step of autophagy and the endocytic pathway as a Beclin-1-binding partner,but little is known regarding the role of Rubicon during viral infection.Here,we performed functional studies of the identified target in interferon(IFN)signaling pathways associated with Rubicon to elucidate the mechanisms of viral resistance to IFN.The Rubicon protein levels were elevated in peripheral blood mononuclear cells,sera and liver tissues from patients with hepatitis B virus(HBV)infection relative to those in healthy individuals.Assays of the overexpression and knockdown of Rubicon showed that Rubicon significantly promoted HBV replication.In addition,Rubicon knockdown resulted in the inhibition of enterovirus 71,influenza A virus and vesicular stomatitis virus.The expression o0f Rubicon led to the suppression of virus-induced type-I interferon(IFN-αand IFN-β)and type-III interferon(IFN-λ1).Translocation of activated IRF3 and IRF7 from the cytoplasm to the nucleus was involved in this process,and the NF-κB essential modulator(NEMO),a key factor in the IFN pathway,was the target with which Rubicon interacted.Our results reveal a previously unrecognized function of Rubicon as a virus-induced protein that binds to NEMO,leading to the inhibition of type-I interferon production.Rubicon thus functions as an important negative regulator of the innate immune response,enhances viral replication and may play a role in viral immune evasion.

Dickkopf-1 contributes to hepatocellular carcinoma tumorigenesis by activating the Wnt/β-catenin signaling pathway

Dysregulation of dickkopf-related protein 1(DKK1)expression has been reported in a variety of human cancers.We previously reported that DKK1 was upregulated in hepatocellular carcinoma(HCC).However,the role of DKK1 in HCC remains unclear.This study aimed to investigate the clinical significance and biological functions of DKK1 in HCC.The expression of DKK1 was examined in cirrhotic and HCC tissues by immunohistochemistry and quantitative real-time polymerase chain reaction(qRT-PCR).DKK1 was silenced or overexpressed in HCC cell lines,and in vitro and in vivo studies were performed.Immunohistochemistry revealed that DKK1 was weakly expressed in cirrhotic tissues(8/22,36.4%)but upregulated in HCC tissues(48/53,90.6%,cohort 1).Significant upregulation of DKK1 was observed in 57.6%(19/33,cohort 2)of HCC tissues by qRT-PCR,and the expression of DKK1 was associated with tumor size(P=0.024)and tumor number(P=0.019).Genetic depletion of DKK1 impaired the proliferation,colony-forming ability,invasion,and tumor formation of HCC cells(HepG2 and HUH-7).Conversely,forced expression of DKK1 increased the proliferation,colony-forming ability,and invasion of HepG2 and HUH-7 cells in vitro and enhanced tumor formation in vivo.Subsequent investigation revealed that the DKK1-mediated proliferation and tumorigenicity of HepG2 and HUH-7 cells is dependent on the Wnt/β-catenin signaling pathway.These findings indicate that DKK1 plays an oncogenic role in HCC by activating the Wnt/β-catenin signaling pathway.

HBeAg induces liver sinusoidal endothelial cell activation to promote intrahepatic CD8 T cell immunity and HBV clearance

To the Editor It is believed that the inherent tolerogenic property of the liver is involved in the chronicity of hepatitis B virus(HBV)infection[1].However,exposure to HBV in adults usually leads to spontaneous clearance of the virus and the induction of potent and effective anti-HBV T cell immunity in the liver[2],suggesting that the immune microenvironment of the liver switches from limiting to allowing effector T cell responses during acute resolution of HBV infection.

Controversial: Early Innate Responses to Hepatitis B Virus Infection,an Explanation for Viral Persistence?

Hepatitis B virus(HBV)infection is one of the most common causes for liver related morbidity and mortality worldwide.Liver fibrosis and cirrhosis occur in the course of chronic HBV infection,with the increasing risk to develop hepatocellular carcinoma.In about 95%of adults’acute hepatitis B virus infection is self-limited,whereas in 90%of young children HBV infection leads to chronic progression.It is likely that a fully developed immune system contributes to HBV clearance(Dandri and Locarnini 2012;Bertoletti and Kennedy 2015).