Interleukin 23 Promotes Hepatocellular Carcinoma Metastasis via NF-Kappa B Induced Matrix Metalloproteinase 9 Expression

Background Hepatocellular carcinoma (HCC) is one of the most popular cancers in the world with poor prognosis, which often develops from chronic liver inflammatory diseases. Interleukin 23 (IL-23) is an inflammatory cytokine which is reported to play an important role in tumor development in animal model. While the function of IL-23 in HCC development remains unknown, so we investigate the role of IL-23 in HCC progression in this study. Methodology and Principal Finding Transcript level of IL-23, interleukin17A (IL-17A) and matrix metalloproteinases 9 (MMP9) in clinical HCC samples (n = 81) was determined by qPCR. Protein expression pattern of IL-23 in primary and metastatic HCC tissues pairs (n = 49 pairs) was determined by immunohistochemistry staining. Cell migration, invasion, RNA interfering and immune blotting were used to characterize the functional and signaling mechanisms in IL-23-treated HCC. Compared with paired non-tumor tissue, higher IL-23 expression was detected in HCC tumor tissues with metastasis. Immunohistochemistry staining confirmed the high expression of IL-23 in metastasis HCC. Immune blotting demonstrated that IL-23 was highly expressed in HCC cell lines with metastasis. Functional study found that IL-23 could promote HCC cell migration and invasion. Molecular analysis revealed that IL-23 could upregulate MMP9 expression via NF-κB/p65 signaling activation and IL-17A could improve IL-23 expression in tumor cells directly via activating NF-κB/p65 signaling pathway. Conclusions IL-23 could promote HCC metastasis by the upregulation of MMP9 expression via activating NF-κB/p65 signaling pathway. At the same time, IL-17A could further promote IL-23 expression in HCC tumor cells.

• Publication year

  2012

• Venue

  PLoS ONE

• Publication date

  2012-09-25

• Fields of study

  Biology, Medicine

• Identifiers
  DOI 10.1371/journal.pone.0046264PMID 23050001PMCID 3457978
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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  2011cited by this paper
• IL-23 suppresses innate immune response independently of IL-17A during carcinogenesis and metastasis

  2010cited by this paper
• Matrix metalloproteinases contribute distinct roles in neuroendocrine prostate carcinogenesis, metastasis, and angiogenesis progression.

  2010cited by this paper
• Overexpression of eukaryotic initiation factor 5A2 enhances cell motility and promotes tumor metastasis in hepatocellular carcinoma

  2010cited by this paper
• Overexpression of EphA2, MMP‐9, and MVD‐CD34 in hepatocellular carcinoma: Implications for tumor progression and prognosis

  2009cited by this paper
• Regulation of the IL-23 and IL-12 balance by Stat3 signaling in the tumor microenvironment.

  2009influential reference
• Microenvironmental regulation of metastasis

  2009cited by this paper
• Increased regulatory T cells correlate with CD8 T-cell impairment and poor survival in hepatocellular carcinoma patients.

  2007cited by this paper
• IL-23 promotes tumour incidence and growth

  2006influential reference
• IL-23 drives a pathogenic T cell population that induces autoimmune inflammation

  2005cited by this paper
• Interleukin-17 family members and inflammation.

  2004cited by this paper
• IL‐12 and IL‐23: master regulators of innate and adaptive immunity

  2004cited by this paper
• Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis.

  2004cited by this paper
• Novel p19 protein engages IL-12p40 to form a cytokine, IL-23, with biological activities similar as well as distinct from IL-12.

  2000influential reference
• The transcription factor Snail controls epithelial–mesenchymal transitions by repressing E-cadherin expression

  2000cited by this paper
• Synergistic upregulation of metalloproteinase‐9 by growth factors and inflammatory cytokines: an absolute requirement for transcription factor NF‐κB

  1998cited by this paper

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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2024cites this paper
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  2023cites this paper
• Multifaceted role of NF-κB in hepatocellular carcinoma therapy: Molecular landscape, therapeutic compounds and nanomaterial approaches.

  2023cites this paper
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  2023cites this paper
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  2023cites this paper
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• Chronic inflammation and cancer; the two sides of a coin.

  2023cites this paper
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  2022cites this paper
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  2022cites this paper
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  2021cites this paper
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  2021cites this paper
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  2021cites this paper
• Systematic Review of the Roles of Interleukins in Hepatocellular Carcinoma.

  2020cites this paper
• Tidrakizumab

  2020cites this paper
• Blood-based inflammation biomarkers of neurocognitive impairment in people living with HIV

  2020cites this paper
• New insights into the IL-12 and IL-23: from a molecular basis to clinical application in immune-mediated inflammation and cancers.

  2020cites this paper
• The Interplay among miRNAs, Major Cytokines, and Cancer-Related Inflammation

  2020cites this paper
• Recent Patents on Anticancer Potential of Helenalin.

  2020cites this paper
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  2020cites this paper
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  2019cites this paper
• Chronic inflammation: key player and biomarker-set to predict and prevent cancer development and progression based on individualized patient profiles

  2019cites this paper
• The role of innate lymphoid cells in selected disease states – cancer formation, metabolic disorder and inflammation

  2019cites this paper
• HNF4α-deficient Fatty Liver Provides a Permissive Environment for Sex-independent Hepatocellular Carcinoma.

  2019cites this paper
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  2019cites this paper
• NCR− group 3 innate lymphoid cells orchestrate IL-23/IL-17 axis to promote hepatocellular carcinoma development

  2019cites this paper
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  2019cites this paper
• Interleukin-23 promotes the migration and invasion of gastric cancer cells by inducing epithelial-to-mesenchymal transition via the STAT3 pathway.

  2018cites this paper
• MicroRNA-221 induces autophagy through suppressing HDAC6 expression and promoting apoptosis in pancreatic cancer.

  2018cites this paper
• Interleukin (IL)-12 and IL-23 and Their Conflicting Roles in Cancer.

  2018influential citation
• IL‑23 concentration‑dependently regulates T24 cell proliferation, migration and invasion and is associated with prognosis in patients with bladder cancer

  2018cites this paper
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  2018cites this paper
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  2018cites this paper
• Differential Serum Cytokine Profiles in Patients with Chronic Hepatitis B, C, and Hepatocellular Carcinoma

  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
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  2017cites this paper
• The Yin and Yang of Innate Lymphoid Cells in Cancer.

  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2016cites this paper
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  2015cites this paper
• IL-12 and IL-23 cytokines: from discovery to targeted therapies for immune-mediated inflammatory diseases

  2015cites this paper
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  2015cites this paper
• [Interleukin-23 strengthens the anti-apoptotic and drug resistance of human tongue squamous cell carcinoma through the Wingless-related integration site/β-catenin pathway].

  2015cites this paper
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  2015cites this paper
• The IL-23 to IL-17 cascade inflammation-related cancers.

  2015cites this paper
• MicroRNA-221 governs tumor suppressor HDAC6 to potentiate malignant progression of liver cancer.

  2015cites this paper
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  2015cites this paper
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  2015cites this paper
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  2015cites this paper
• miR-221/222 induces pancreatic cancer progression through the regulation of matrix metalloproteinases

  2015cites this paper
• Role of IL-17F T7488C polymorphism in carcinogenesis: a meta-analysis

  2014cites this paper
• CD68(+)HLA-DR(+) M1-like macrophages promote motility of HCC cells via NF-κB/FAK pathway.

  2014cites this paper
• MicroRNA-206 overexpression promotes apoptosis, induces cell cycle arrest and inhibits the migration of human hepatocellular carcinoma HepG2 cells

  2014cites this paper
• Licochalcone A Suppresses Migration and Invasion of Human Hepatocellular Carcinoma Cells through Downregulation of MKK4/JNK via NF-κB Mediated Urokinase Plasminogen Activator Expression

  2014cites this paper
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  2014cites this paper
• Icaritin suppresses the proliferation of human osteosarcoma cells in vitro by increasing apoptosis and decreasing MMP expression

  2014cites this paper
• IL-23 selectively promotes the metastasis of colorectal carcinoma cells with impaired Socs3 expression via the STAT5 pathway.

  2014cites this paper
• IL-12-and IL-23 in health and disease.

  2014cites this paper
• Extracts of Celastrus orbiculatus exhibit anti-proliferative and anti-invasive effects on human gastric adenocarcinoma cells

  2014cites this paper
• Prostaglandin E2 stimulates β1-integrin expression in hepatocellular carcinoma through the EP1 receptor/PKC/NF-κB pathway

  2014cites this paper
• TNF‐α mediates mitochondrial uncoupling and enhances ROS‐dependent cell migration via NF‐κB activation in liver cells

  2014cites this paper
• Interleukin-10 Superfamily and Cancer

  2014cites this paper
• Prostaglandin E 2 stimulates b 1-integrin expression in hepatocellular carcinoma through the EP 1 receptor / PKC / NFk B pathway

  2014cites this paper
• The therapeutic value of targeting inflammation in gastrointestinal cancers.

  2014cites this paper
• Opposing functions of psoriasin (S100A7) and koebnerisin (S100A15) in epithelial carcinogenesis.

  2013cites this paper
• miR-224 is Critical for Celastrol-Induced Inhibition of Migration and Invasion of Hepatocellular Carcinoma Cells

  2013cites this paper
• A balance of interleukin-12 and -23 in cancer.

  2013cites this paper
• Inflammation and liver tumorigenesis

  2013cites this paper
• Highly synergistic effect of sequential treatment with epigenetic and anticancer drugs to overcome drug resistance in breast cancer cells is mediated via activation of p21 gene expression leading to G2/M cycle arrest.

  2013cites this paper
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  2013cites this paper