ArticleImmune network2021
Hepatitis B virus X Protein Promotes Liver Cancer Progression through Autophagy Induction in Response to TLR4 Stimulation.
Article in Immune network, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- GLDC interacts with VPS34 to inhibit tumorigenesis and epithelial-mesenchymal transition in hepatocellular carcinoma.Pharmaceutical science advances · 2025Article
- TXNIP Suppresses Lung Cancer Progression by Inhibiting TRAF6-Mediated NF-κB Activation and Autophagy.Immune network · 2025Article
- Hepatitis B Virus X Protein Upregulates SREBP2 to Modulate Autophagy in Hepatocellular Carcinoma.Cancer medicine · 2025Article
- Prediction of Ki-67 expression in hepatocellular carcinoma with machine learning models based on intratumoral and peritumoral radiomic features.World journal of gastrointestinal oncology · 2025Article
- The Malignant Transformation of Viral Hepatitis to Hepatocellular Carcinoma: Mechanisms and Interventions.MedComm · 2025Review
- Differential profiles of autophagy and Nrf2-mediated antioxidant response in HBeAg-positive versus HBeAg-negative chronic hepatitis B patients.Frontiers in microbiology · 2025Article
- Hepatitis B virus X protein (HBx)-mediated immune modulation and prognostic model development in hepatocellular carcinoma.PloS one · 2025Article
- USP21-EGFR signaling axis is functionally implicated in metastatic colorectal cancer.Cell death discovery · 2024Article
- IPEC-J2 Autophagy Induced by TLR4 and NSP6 Interactions Facilitate Porcine Epidemic Diarrhea Virus Replication.Viruses · 2024Article
- Crosstalk between Dysfunctional Mitochondria and Proinflammatory Responses during Viral Infections.International journal of molecular sciences · 2024Review
- The oncogenic role of hepatitis B virus X gene in hepatocarcinogenesis: recent updates.Exploration of targeted anti-tumor therapy · 2024Review
- Tumor Necrosis Factor Receptor-Associated Factor 6 and Human Cancer: A Systematic Review of Mechanistic Insights, Functional Roles, and Therapeutic Potential.Journal of Cancer · 2024Review
- Tumor-associated macrophages and CD8+ T cells: dual players in the pathogenesis of HBV-related HCC.Frontiers in immunology · 2024Review
- β-arrestin 2 negatively regulates lung cancer progression by inhibiting the TRAF6 signaling axis for NF-κB activation and autophagy induced by TLR3 and TLR4.Cell death & disease · 2023Article
- FFAR2 antagonizes TLR2- and TLR3-induced lung cancer progression via the inhibition of AMPK-TAK1 signaling axis for the activation of NF-κB.Cell & bioscience · 2023Article
- The Role of TLR4 in the Immunotherapy of Hepatocellular Carcinoma: Can We Teach an Old Dog New Tricks?Cancers · 2023Review
- rt269L-Type hepatitis B virus (HBV) in genotype C infection leads to improved mitochondrial dynamics via the PERK-eIF2α-ATF4 axis in an HBx protein-dependent manner.Cellular & molecular biology letters · 2023Article
- Vitamin D Attenuates Pain and Cartilage Destruction in OA Animals via Enhancing Autophagic Flux and Attenuating Inflammatory Cell Death.Immune network · 2022Article
- Stratifin (SFN) regulates lung cancer progression via nucleating the Vps34-BECN1-TRAF6 complex for autophagy induction.Clinical and translational medicine · 2022Article
- Review
Corrections and comments
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hepatitis B virus X (HBx) protein has been reported as a key protein regulating the pathogenesis of HBV-induced hepatocellular carcinoma (HCC). Recent evidence has shown that HBx is implicated in the activation of autophagy in hepatic cells. Nevertheless, the precise molecular and cellular mechanism by which HBx induces autophagy is still controversial. Herein, we investigated the molecular and cellular mechanism by which HBx is involved in the TRAF6-BECN1-Bcl-2 signaling for the regulation of autophagy in response to TLR4 stimulation, therefore influencing the HCC progression. HBx interacts with BECN1 (Beclin 1) and inhibits the association of the BECN1-Bcl-2 complex, which is known to prevent the assembly of the pre-autophagosomal structure. Furthermore, HBx enhances the interaction between VPS34 and TRAF6-BECN1 complex, increases the ubiquitination of BECN1, and subsequently enhances autophagy induction in response to LPS stimulation. To verify the functional role of HBx in liver cancer progression, we utilized different HCC cell lines, HepG2, SK-Hep-1, and SNU-761. HBx-expressing HepG2 cells exhibited enhanced cell migration, invasion, and cell mobility in response to LPS stimulation compared to those of control HepG2 cells. These results were consistently observed in HBx-expressed SK-Hep-1 and HBx-expressed SNU-761 cells. Taken together, our findings suggest that HBx positively regulates the induction of autophagy through the inhibition of the BECN1-Bcl-2 complex and enhancement of the TRAF6-BECN1-VPS34 complex, leading to enhance liver cancer migration and invasion.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.