ArticleOncotarget2015
Hypoxia up-regulates SERPINB3 through HIF-2α in human liver cancer cells.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 60 citations in OpenAlex.
- Regulatory mechanism of the RNF168-SCCA1-MYH9 signaling axis in the response of ulcerative colitis.Journal of gastroenterology · 2026Article
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- Protease activated receptor 2 as a novel druggable target for the treatment of metabolic dysfunction-associated fatty liver disease and cancer.Frontiers in immunology · 2024Review
- SERPINB3-MYC axis induces the basal-like/squamous subtype and enhances disease progression in pancreatic cancer.Cell reports · 2023Article
- Review
- Article
- Identification and validation of a dysregulated TME-related gene signature for predicting prognosis, and immunological properties in bladder cancer.Frontiers in immunology · 2023Article
- Pathogenesis and Current Treatment Strategies of Hepatocellular Carcinoma.Biomedicines · 2022Review
- SerpinB3 administration protects liver against ischemia-reperfusion injury.European journal of histochemistry : EJH · 2022Article
- SerpinB3 drives cancer stem cell survival in glioblastoma.Cell reports · 2022Article
- Hepatic Myofibroblasts: A Heterogeneous and Redox-Modulated Cell Population in Liver Fibrogenesis.Antioxidants (Basel, Switzerland) · 2022Review
- Sirtuins and Hypoxia in EMT Control.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Oncostatin M is overexpressed in NASH-related hepatocellular carcinoma and promotes cancer cell invasiveness and angiogenesis.The Journal of pathology · 2022Article
- Hyaluronated and PEGylated Liposomes as a Potential Drug-Delivery Strategy to Specifically Target Liver Cancer and Inflammatory Cells.Molecules (Basel, Switzerland) · 2022Article
- HIF2α Activation in NASH: A New Force Pushing Toward HCC.Cellular and molecular gastroenterology and hepatology · 2022Article
- Effects of Sensitized Sorafenib with a Paeoniflorin and Geniposide Mixture on Liver Cancer via the NF-Evidence-based complementary and alternative medicine : eCAM · 2022Article
- SerpinB3 as a Pro-Inflammatory Mediator in the Progression of Experimental Non-Alcoholic Fatty Liver Disease.Frontiers in immunology · 2022Article
- Deciphering the Molecular Mechanism of Red Raspberry in Apoptosis of Liver Cancer Cells.Evidence-based complementary and alternative medicine : eCAM · 2022Article
- GPR21 Inhibition Increases Glucose-Uptake in HepG2 Cells.International journal of molecular sciences · 2021Article
- Review
Corrections and comments
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Authors and funding
20 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
SERPINB3 is a cysteine-proteases inhibitor up-regulated in a significant number of cirrhotic patients carrying hepatocellular carcinoma (HCC) and recently proposed as a prognostic marker for HCC early recurrence. SERPINB3 has been reported to stimulate proliferation, inhibit apoptosis and, similar to what reported for hypoxia, to trigger epithelial-to-mesenchymal transition (EMT) and increased invasiveness in liver cancer cells. This study has investigated whether SERPINB3 expression is regulated by hypoxia-related mechanisms in liver cancer cells. Exposure of HepG2 and Huh7 cells to hypoxia up-regulated SERPINB3 transcription, protein synthesis and release in the extracellular medium. Hypoxia-dependent SERPINB3 up-regulation was selective (no change detected for SERPINB4) and operated through hypoxia inducible factor (HIF)-2α (not HIF-1α) binding to SERPINB3 promoter, as confirmed by chromatin immuno-precipitation assay and silencing experiments employing specific siRNAs. HIF-2α-mediated SERPINB3 up-regulation under hypoxic conditions required intracellular generation of ROS. Immuno-histochemistry (IHC) and transcript analysis, performed in human HCC specimens, revealed co-localization of the two proteins in liver cancer cells and the existence of a positive correlation between HIF-2α and SERPINB3 transcript levels, respectively. Hypoxia, through HIF-2α-dependent and redox-sensitive mechanisms, up-regulates the transcription, synthesis and release of SERPINB3, a molecule with a high oncogenic potential.
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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 OpenQuestion graph.