ArticleOncotarget2016
Hypoxia inducible factor-1 mediates the expression of the immune checkpoint HLA-G in glioma cells through hypoxia response element located in exon 2.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
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Who cites it
43 citing papers in PubMed, 67 citations in OpenAlex.
- Human leukocyte antigen-G in hepatocellular carcinoma driven by chronic viral hepatitis or steatotic liver disease.Scientific reports · 2025Article
- A prognostic model for stomach adenocarcinoma based on hypoxia- and immune-related genes.Archives of medical science : AMS · 2025Article
- Recent advances in immunotherapy for gliomas: overcoming barriers and advancing precision strategies.Frontiers in immunology · 2025Review
- Natural killer cells in cancer immunotherapy.MedComm · 2024Review
- Associations between HIFs and tumor immune checkpoints: mechanism and therapy.Discover oncology · 2024Review
- Mechanisms of HIF-driven immunosuppression in tumour microenvironment.Journal of the Egyptian National Cancer Institute · 2023Review
- HIF: a master regulator of nutrient availability and metabolic cross-talk in the tumor microenvironment.The EMBO journal · 2023Review
- Molecular landscapes of glioblastoma cell lines revealed a group of patients that do not benefit fromFrontiers in neuroscience · 2023Article
- Article
- Doxorubicin induced immune abnormalities and inflammatory responses via HMGB1, HIF1-α and VEGF pathway in progressive of cardiovascular damage.Annals of medicine and surgery (2012) · 2022Review
- HLA-G and Other Immune Checkpoint Molecules as Targets for Novel Combined Immunotherapies.International journal of molecular sciences · 2022Review
- Differentially Expressed Bone Marrow microRNAs Are Associated With Soluble HLA-G Bone Marrow Levels in Childhood Leukemia.Frontiers in genetics · 2022Article
- Prediction of immunotherapy efficacy and immunomodulatory role of hypoxia in colorectal cancer.Therapeutic advances in medical oncology · 2022Review
- Molecular subtypes of cuproptosis regulators and their correlation with clinical prognosis and immune response in glioma.American journal of translational research · 2022Article
- Structural Characterization of the Interaction of Hypoxia Inducible Factor-1 with Its Hypoxia Responsive Element at the -964G > A Variation Site of theInternational journal of molecular sciences · 2021Article
- HLA-G genetic diversity and evolutive aspects in worldwide populations.Scientific reports · 2021Article
- A Review of the Role of Hypoxia in Radioresistance in Cancer Therapy.Medical science monitor : international medical journal of experimental and clinical research · 2021Review
- Integration of Epigenetic Mechanisms into Non-Genotoxic Carcinogenicity Hazard Assessment: Focus on DNA Methylation and Histone Modifications.International journal of molecular sciences · 2021Review
- Article
- Scouting for common genes in the heterogenous hypoxic tumor microenvironment and their validation in glioblastoma.3 Biotech · 2021Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
HLA-G is an immune checkpoint molecule with specific relevance in cancer immunotherapy. It was first identified in cytotrophoblasts, protecting the fetus from maternal rejection. HLA-G tissue expression is very restricted but induced in numerous malignant tumors such as glioblastoma, contributing to their immune escape. Hypoxia occurs during placenta and tumor development and was shown to activate HLA-G. We aimed to elucidate the mechanisms of HLA-G activation under conditions combining hypoxia-mimicking treatment and 5-aza-2'deoxycytidine, a DNA demethylating agent used in anti-cancer therapy which also induces HLA-G. Both treatments enhanced the amount of HLA-G mRNA and protein in HLA-G negative U251MG glioma cells. Electrophoretic Mobility Shift Assays and luciferase reporter gene assays revealed that HLA-G upregulation depends on Hypoxia Inducible Factor-1 (HIF-1) and a hypoxia responsive element (HRE) located in exon 2. A polymorphic HRE at -966 bp in the 5'UT region may modulate the magnitude of the response mediated by the exon 2 HRE. We suggest that therapeutic strategies should take into account that HLA-G expression in response to hypoxic tumor environment is dependent on HLA-G gene polymorphism and DNA methylation state at the HLA-G locus.
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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.