Stimulation of Interferon-Stimulated Gene 20 by Thyroid Hormone Enhances Angiogenesis in Liver Cancer
| العنوان: | Stimulation of Interferon-Stimulated Gene 20 by Thyroid Hormone Enhances Angiogenesis in Liver Cancer |
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| المؤلفون: | Tzu-Kang Lin, Sheng-Ming Wu, I-Hsiao Chung, Syuan-Ling Lin, Chau-Ting Yeh, Yang-Hsiang Lin, Hsiang-Cheng Chi, Kwang-Huei Lin, Ching-Ying Chen |
| المصدر: | Neoplasia (New York, N.Y.) Neoplasia: An International Journal for Oncology Research, Vol 20, Iss 1, Pp 57-68 (2018) |
| بيانات النشر: | Elsevier BV, 2018. |
| سنة النشر: | 2018 |
| مصطلحات موضوعية: | Exonucleases, 0301 basic medicine, IHC, Immunohistochemistry, Cancer Research, HCC, Hepatocellular carcinoma, Endostatin, Collagen XVIII, Angiogenesis, Cellular differentiation, VEGF, Vascular endothelial growth factor, Gene Expression, Kaplan-Meier Estimate, IGFBP-3, Insulin-like growth factor binding protein-3, Metastasis, Gene Knockout Techniques, ChIP, Chromatin immunoprecipitation, TR, Thyroid receptors, EMT, Epithelial-mesenchymal transition, AR, Amphiregulin, T3, Thyroid hormone, TF, Coagulation factor III, ISG20, Interferon-stimulated gene 20 kDa, CM, Conditional medium, Regulation of gene expression, TSP-1, Thrombospondin-1, Neovascularization, Pathologic, Liver Neoplasms, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Gene Expression Regulation, Neoplastic, HUVEC, Human umbilical vein endothelial cell, TRE, Thyroid hormone response element, Signal Transduction, IL-8, Interleukin-8, Thyroid Hormones, Original article, RFS, Recurrence-free survival, Carcinoma, Hepatocellular, TSS, Transcription start site, Biology, lcsh:RC254-282, Thyroid hormone receptor beta, 03 medical and health sciences, Cell Line, Tumor, medicine, Humans, Thyroid hormone receptor, Interferon-stimulated gene, Interleukin-8, medicine.disease, 030104 developmental biology, Tumor progression, Exoribonucleases, Cancer research |
| الوصف: | Thyroid hormone, 3,3′,5-triiodo-l-thyronine (T3), mediates several physiological processes, including embryonic development, cellular differentiation and cell proliferation, via binding to its nuclear thyroid receptors (TR). Previous microarray and Chromatin immunoprecipitation (ChIP)-on-ChIP analyses have revealed that interferon-stimulated gene 20 kDa (ISG20), an exoribonuclease involved in the antiviral function of interferon, is up-regulated by T3 in HepG2-TR cells. However, the underlying mechanisms of ISG20 action in tumor progression remain unknown to date. Here, we verified induction of ISG20 mRNA and protein expression by T3 in HepG2-TR cells. Based on the ChIP-on-ChIP database, potential thyroid hormone responsive element of the ISG20 promoter region was predicted, and the result confirmed with the ChIP assay. Functional assays showed that forced expression of ISG20 leads to significant promotion of metastasis and angiogenesis, both in vitro and in vivo. Furthermore, the angiogenic-related protein, interleukin-8 (IL-8), was up-regulated through a T3-mediated increase in ISG20, as determined using a human angiogenesis array kit. Induction of IL-8 signaling activated the p-JAK2/p-STAT3 pathway, in turn, leading to promotion of tumor metastasis and angiogenesis. Furthermore, ISG20 overexpression in hepatocellular carcinoma (HCC) specimens was positively correlated with clinical parameters, including vascular invasion, α-fetoprotein and tumor size. Higher ISG20 expression was significantly correlated with poorer recurrence-free survival in HCC patients. Our results collectively indicate higher TR-dependent expression of ISG20 in a subset of HCC, supporting an oncogenic role in HCC progression. |
| تدمد: | 1476-5586 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::d127ac9c5ce2d53a05e25a3364010609Test https://doi.org/10.1016/j.neo.2017.10.007Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....d127ac9c5ce2d53a05e25a3364010609 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765586 |
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