Hepatitis B virus X reduces hepatocyte apoptosis and promotes cell cycle progression through the Akt/mTOR pathway in vivo

Wang, Handong; Huo, Bennian; Liu, Jie; Huang, Xin; Zhang, Siyao; Feng, Tao

doi:10.1016/j.gene.2018.12.054

Cited by 16 publications

(16 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Furthermore, HBx upregulates the expression of AFPR and AFP, which are early indicators of HBx-driven hepatocarcinogenesis, to activate the PI3K/Akt/mTOR signaling pathway (Zhu et al 2015(Zhu et al , 2017. Moreover, the HBx-induced antiapoptotic mechanism is essential for promoting the malignant transformation of hepatocytes via activation of the PI3K/ Akt/mTOR signaling pathway (Wang X et al 2019). The weakness of these studies is that the expression levels of HBx protein in transfected cells may be higher than that during HBV infection and replication and cause nonphysiological effects.…”

Section: Role Of Hbx In the Mtor Signaling Pathwaymentioning

confidence: 99%

“…Previous studies have shown that the interaction of mTOR signaling pathway and HBV life cycle is complex. While HBV proteins like the HBV X (HBx) protein are able to modulate this pathway (Zhu et al 2017;Wang X et al 2019). HBV replication and gene expression are also regulated by the mTOR signaling pathway (Guo et al 2007b;Zhang et al 2011;Huang et al 2014;Li et al 2015;Lin et al 2017;Wang et al 2020aWang et al , 2020b.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication

et al. 2021

View full text Add to dashboard Cite

Mammalian target of rapamycin (mTOR) is a conserved Ser/Thr kinase that includes mTOR complex (mTORC) 1 and mTORC2. The mTOR pathway is activated in viral hepatitis, including hepatitis B virus (HBV) infection-induced hepatitis. Currently, chronic HBV infection remains one of the most serious public health issues worldwide. The unavailability of effective therapeutic strategies for HBV suggests that clarification of the pathogenesis of HBV infection is urgently required. Increasing evidence has shown that HBV infection can activate the mTOR pathway, indicating that HBV utilizes or hijacks the mTOR pathway to benefit its own replication. Therefore, the mTOR signaling pathway might be a crucial target for controlling HBV infection. Here, we summarize and discuss the latest findings from model biology research regarding the interaction between the mTOR signaling pathway and HBV replication.

show abstract

Section: Role Of Hbx In the Mtor Signaling Pathwaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Hepatic overexpression of HBV X protein (HBx) activates AKT and mTORC1 signaling (116,117) and induces the expression of α-fetoprotein (AFP), which attenuates the function of phosphatase and tensin homolog (PTEN) leading to increased AKT-mTORC1 signaling in HBxtransfected human liver cells and HCC (118). This AFPmediated mechanism also promotes the initiation of HCC progenitor/stem cells (119).…”

Section: Hbv and Hcvmentioning

confidence: 99%

Dairy consumption and hepatocellular carcinoma risk

Melnik¹

2021

Ann Transl Med

View full text Add to dashboard Cite

This review provides epidemiological and translational evidence for milk and dairy intake as critical risk factors in the pathogenesis of hepatocellular carcinoma (HCC). Large epidemiological studies in the United States and Europe identified total dairy, milk and butter intake with the exception of yogurt as independent risk factors of HCC. Enhanced activity of mechanistic target of rapamycin complex 1 (mTORC1) is a hallmark of HCC promoted by hepatitis B virus (HBV) and hepatitis C virus (HCV). mTORC1 is also activated by milk protein-induced synthesis of hepatic insulin-like growth factor 1 (IGF-1) and branched-chain amino acids (BCAAs), abundant constituents of milk proteins. Over the last decades, annual milk protein-derived BCAA intake increased 3 to 5 times in Western countries. In synergy with HBV-and HCV-induced secretion of hepatocyte-derived exosomes enriched in microRNA-21 (miR-21) and miR-155, exosomes of pasteurized milk as well deliver these oncogenic miRs to the human liver. Thus, milk exosomes operate in a comparable fashion to HBV-or HCV-induced exosomes. Milk-derived miRs synergistically enhance IGF-1-AKT-mTORC1 signaling and promote mTORC1-dependent translation, a meaningful mechanism during the postnatal growth phase, but a long-term adverse effect promoting the development of HCC. Both, dietary BCAA abundance combined with oncogenic milk exosome exposure persistently overstimulate hepatic mTORC1. Chronic alcohol consumption as well as type 2 diabetes mellitus (T2DM), two HCC-related conditions, increase BCAA plasma levels. In HCC, mTORC1 is further hyperactivated due to RAB1 mutations as well as impaired hepatic BCAA catabolism, a metabolic hallmark of T2DM. The potential HCC-preventive effect of yogurt may be caused by lactobacilli-mediated degradation of BCAAs, inhibition of branched-chain α-ketoacid dehydrogenase kinase via production of intestinal medium-chain fatty acids as well as degradation of milk exosomes including their oncogenic miRs. A restriction of total animal protein intake realized by a vegetable-based diet is recommended for the prevention of HCC.

show abstract

“…Yen et al reported that the HBx-activated mTOR signaling proceeds via IκB kinase β (IKKβ) and increases cell proliferation and vascular endothelial growth factor (VEGF) production during HCC development [28]. HBx also induces anti-apoptotic proteins and promotes cell cycle progression in hepatocytes in vivo by activating the mTOR signaling pathway [30]. Yang et al found that HBV wild-type or mutant pre-S2 proteins enhance VEGF-A expression and activate mTOR signaling in ground glass hepatocytes (GGHs) of chronic HBV carriers [31].…”

Section: Hbv Induces the Initiation Of Autophagymentioning

confidence: 99%

Interplay between Cellular Autophagy and Hepatitis B Virus Replication: A Systematic Review

Lin

Zhao

Huang

et al. 2020

Cells

View full text Add to dashboard Cite

Autophagy, a conserved process in which cells break down and destroy old, damaged, or abnormal proteins and other substances in the cytoplasm through lysosomal degradation, occurs via autophagosome formation and aids in the maintenance of intracellular homeostasis. Autophagy is closely associated with hepatitis B virus (HBV) replication and assembly. Currently, HBV infection is still one of the most serious public health issues worldwide. The unavailability of satisfactory therapeutic strategies for chronic HBV infection indicates an urgent need to elucidate the mechanisms underlying the pathogenesis of HBV infection. Increasing evidence has shown that HBV not only possesses the ability to induce incomplete autophagy but also evades autophagic degradation, indicating that HBV utilizes or hijacks the autophagy machinery for its own replication. Therefore, autophagy might be a crucial target pathway for controlling HBV infection. The definite molecular mechanisms underlying the association between cellular autophagy and HBV replication require further clarification. In this review, we have summarized and discussed the latest findings on the interplay between autophagy and HBV replication.

show abstract

Hepatitis B virus X reduces hepatocyte apoptosis and promotes cell cycle progression through the Akt/mTOR pathway in vivo

Cited by 16 publications

References 39 publications

mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication

mTOR Signaling: The Interface Linking Cellular Metabolism and Hepatitis B Virus Replication

Dairy consumption and hepatocellular carcinoma risk

Interplay between Cellular Autophagy and Hepatitis B Virus Replication: A Systematic Review

Contact Info

Product

Resources

About