ArticleJournal of experimental & clinical cancer research : CR2019
Hypoxia-inducible gene 2 promotes the immune escape of hepatocellular carcinoma from nature killer cells through the interleukin-10-STAT3 signaling pathway.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 51 citations in OpenAlex.
- Construction of a Prognostic Model and Subgroup Characteristics Related to Hypoxia-Immune Evasion in T Cells of Hepatocellular Carcinoma Based on Single-Cell and Bulk RNA Analysis.Journal of hepatocellular carcinoma · 2026Article
- Decoding Hepatocellular Carcinoma Metastasis: Molecular Mechanisms, Targeted Therapies, and Potential Biomarkers.Current issues in molecular biology · 2025Review
- Spatial heterogeneity of the hepatocellular carcinoma microenvironment determines the efficacy of immunotherapy.Discover oncology · 2025Review
- Angiogenesis and Immunosuppressive Niche in Hepatocellular Carcinoma: Reshaping Vascular - Immune Axis to Potentiate antiPD - 1/PD - L1 Therapy.Cancer management and research · 2025Review
- Identification and validation of expression and functions of ferroptosis-related gene HILPDA in early-onset preeclampsia placentas.Frontiers in immunology · 2025Article
- The mTranslational cancer research · 2024Article
- Signaling molecules in the microenvironment of hepatocellular carcinoma.Functional & integrative genomics · 2024Review
- Hypoxic tumor microenvironment: Destroyer of natural killer cell function.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024Article
- Metabolic reprogramming in the tumor microenvironment of liver cancer.Journal of hematology & oncology · 2024Review
- Prognostic Hypoxia-Angiogenesis-Related Gene Signature in Hepatocellular Carcinoma, in Which HILPDA Contributes to Tumor Progression.Journal of inflammation research · 2024Article
- Exploring the JAK/STAT Signaling Pathway in Hepatocellular Carcinoma: Unraveling Signaling Complexity and Therapeutic Implications.International journal of molecular sciences · 2023Review
- HILPDA-mediated lipidomic remodelling promotes radiotherapy resistance in nasopharyngeal carcinoma by accelerating mitophagy.Cellular and molecular life sciences : CMLS · 2023Article
- Hypoxic microenvironment in cancer: molecular mechanisms and therapeutic interventions.Signal transduction and targeted therapy · 2023Review
- Tumor Microenvironment Composition and Related Therapy in Hepatocellular Carcinoma.Journal of hepatocellular carcinoma · 2023Review
- Review
- Novel hypoxia features with appealing implications in discriminating the prognosis, immune escape and drug responses of 947 hepatocellular carcinoma patients.Translational cancer research · 2022Article
- ADAM12 is an independent predictor of poor prognosis in liver cancer.Scientific reports · 2022Article
- Exploration of Different Hypoxia Patterns and Construction of a Hypoxia-Related Gene Prognostic Index in Colorectal Cancer.Frontiers in immunology · 2022Article
- Sublethal hyperthermia enhances anticancer activity of doxorubicin in chronically hypoxic HepG2 cells through ROS-dependent mechanism.Bioscience reports · 2021Article
- Hypoxia, oxidative stress, and immune evasion: a trinity of the trichothecenes T-2 toxin and deoxynivalenol (DON).Archives of toxicology · 2021Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundThe study examines the expression and function of hypoxia-inducible gene 2 (HIG2) in hepatocellular carcinoma (HCC) tissues and cells.
methodsForty patients with HCC were included in the study. Bioinformatic analysis was used to analyze the clinical relevance of HIG2 expression in HCC tissue samples. Immunohistochemistry was employed to determine the expression of target proteins in tumor tissues. Hepatic HepG2 and SMMC-7721 cells were transfected with HIG2-targeting siRNA with Lipofectamine 2000. qRT-PCR was carried out to determine gene expression levels, while Western blotting was used to determine protein expression. A CCK-8 assay was performed to detect proliferation of cells, while migration and invasion of cells were studied by Transwell assay. Flow cytometry was carried out to detect surface markers and effector molecules in Nature killercells, as well as the killing effect of NK cells.
resultsHIG2 expression was upregulated in HCC. Silencing of HIG2 suppressed HCC cell migration and invasion. The killing effect of NK cells on HCC cells was enhanced after HIG2 was silenced in HCC cells. Conditioned media from HIG2-silenced SMMC-7721 cells inhibited the phenotype and function of NK cells. HCC cells with silenced expression of HIG2 modulated the activity of NK cells via STAT3. HIG2 promoted the evasion of HCC cells from killing by NK cells through upregulation of IL-10 expression.
conclusionThe study demonstrates that HIG2 activates the STAT3 signaling pathway in NK cells by promoting IL-10 release by HCC cells, thereby inhibiting the killing activity of NK cells, and subsequently promoting the recurrence and metastasis of HCC.
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