ArticleBMC cancer2015
Downregulation of toll-like receptor 4 induces suppressive effects on hepatitis B virus-related hepatocellular carcinoma via ERK1/2 signaling.
Article in BMC cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 34 citations in OpenAlex.
- Article
- A state-of-the-art review on the NRF2 in Hepatitis virus-associated liver cancer.Cell communication and signaling : CCS · 2023Review
- Targeting TREM1 augments antitumor T cell immunity by inhibiting myeloid-derived suppressor cells and restraining anti-PD-1 resistance.The Journal of clinical investigation · 2023Article
- MicroRNAs based regulation of cytokine regulating immune expressed genes and their transcription factors in COVID-19.Meta gene · 2022Article
- Konjac glucomannan enhances 5-FU-induced cytotoxicity of hepatocellular carcinoma cells via TLR4/PERK/CHOP signaling to induce endoplasmic reticulum stress.Oncology research · 2022Article
- Regulation of Pattern-Recognition Receptor Signaling by HBX During Hepatitis B Virus Infection.Frontiers in immunology · 2022Review
- Radiation‑induced dysfunction of energy metabolism in the heart results in the fibrosis of cardiac tissues.Molecular medicine reports · 2021Article
- The Hepatitis B Virus Interactome: A Comprehensive Overview.Frontiers in microbiology · 2021Review
- Androgen Receptor (AR)-TLR4 Crosstalk Mediates Gender Disparities in Hepatocellular Carcinoma Incidence and Progression.Journal of Cancer · 2020Article
- Hepatitis B virus-X protein regulates high mobility group box 1 to promote the formation of hepatocellular carcinoma.Oncology letters · 2018Article
- Inflammatory factor receptor Toll-like receptor 4 controls telomeres through heterochromatin protein 1 isoforms in liver cancer stem cell.Journal of cellular and molecular medicine · 2018Article
- Role of TLR4 as a prognostic factor for survival in various cancers: a meta-analysis.Oncotarget · 2018Article
- The Key Role of c-Fos for Immune Regulation and Bacterial Dissemination inFrontiers in cellular and infection microbiology · 2018Article
- [Hepatitis B core antigen promotes invasion of hepatocellular carcinoma cell line HepG2.2.15 via Toll-like receptor 4].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2017Article
- Anti-viral role of toll like receptor 4 in hepatitis B virus infection: AnWorld journal of gastroenterology · 2016Article
- Toll-like receptors 1, 2, 4 and 6 in esophageal epithelium, Barrett's esophagus, dysplasia and adenocarcinoma.Oncotarget · 2016Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatitis B virus (HBV) infection is a major risk factor which can lead to development of hepatocellular carcinoma (HCC). In this study, we aimed to explore the effects of toll-like receptor 4 (TLR4) downregulation on the growth and survival of HBV-related HCC cells and to examine the molecular mechanisms been involved.
methodsThe expression levels of TLR4 were examined in a panel of HCC cell lines (HepG2, SMMC7721, Huh7, HepG2.2.15 and Hep3B). The effects of TLR4 downregulation on the proliferation, apoptosis, and tumorigenicity of HBV-related HepG2.2.15 cells were determined. The effects of TLR4 downregulation on multiple signaling pathways were also measured. Co-immunoprecipitation and immunofluoresence staining assays were performed to investigate the interaction between TLR4 and HBV X protein (HBx).
resultsThe mRNA and protein levels of TLR4 were significantly increased in HepG2.2.15 cells than those in the other cells which have been studied. Downregulation of TLR4 significantly decreased the proliferation and induced G2/M cell cycle arrest and apoptosis in HepG2.2.15 cells. TLR4 depletion inhibited HepG2.2.15 cell colony formation and tumor growth in nude mice. TLR4 silencing decreased the phosphorylation of ERK1/2 but not JNK1/2, p38, or NF-κB. Chemical inhibition of ERK1/2 approximately phenocopied the growth-suppressive effect of TLR4 downregulation on HepG2.2.15 cells. In addition, TLR4 showed a physical interaction with HBx.
conclusionsTaken together, TLR4 plays a tumor-promoting role in HBV-related HCC cells, which is associated with regulation of ERK1/2 activation and interaction with HBx. Therefore, TLR4 may be a potential therapeutic target for HBV-related HCC.
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