Vitamin D receptors (VDR), hydroxylases CYP27B1 and CYP24A1 and retinoid-related orphan receptors (ROR) level in human uveal tract and ocular melanoma with different melanization levels.,Scientific Reports

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Vitamin D receptors (VDR), hydroxylases CYP27B1 and CYP24A1 and retinoid-related orphan receptors (ROR) level in human uveal tract and ocular melanoma with different melanization levels.
Scientific Reports ( IF 3.8 ) Pub Date : 2019-06-24 , DOI: 10.1038/s41598-019-45161-8
Anna Markiewicz ₁ , Anna A Brożyna ₂ , Ewa Podgórska ₃ , Martyna Elas ₃ , Krystyna Urbańska ₃ , Anton M Jetten ₄ , Andrzej T Slominski _{5,

6} , Wojciech Jóźwicki _{7,

8} , Jolanta Orłowska-Heitzman ₉ , Grzegorz Dyduch ₉ , Bożena Romanowska-Dixon ₁

Affiliation

Department of Ophthalmology and Ocular Oncology, Medical College, Jagiellonian University in Kraków, 31-501, Kraków, Poland.
Department of Human Biology, Faculty of Biology and Environmental Protection, Nicolaus Copernicus University, 87-100, Toruń, Poland.
Department of Biophysics, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University in Kraków, 31-007, Kraków, Poland.
Cell Biology Section, Immunity, Inflammation, and Disease Laboratory, National Institute of Environmental Health Sciences, National Institutes of Health, Research Triangle Park, NC, 27709, USA.
Department of Dermatology, Comprehensive Cancer Center, Cancer Chemoprevention Program, University of Alabama at Birmingham, Birmingham, AL, 35294, USA.
VA Medical Center, Birmingham, AL, 35294, USA.
Department of Tumor Pathology and Pathomorphology, Oncology Centre - Prof. Franciszek Łukaszczyk Memorial Hospital, Bydgoszcz, Poland.
Department of Tumor Pathology and Pathomorphology, Faculty of Health Sciences, Nicolaus Copernicus University Collegium Medicum in Bydgoszcz, 85-796, Bydgoszcz, Poland.
Clinical and Experimental Pathomorphology, Jagiellonian University, Medical College, 31-531, Kraków, Poland.

In recent years, a significant number of studies have investigated the preventive role of vitamin D in a number of different neoplasms. In this study, we analyze various components of the vitamin D signaling pathways in the human uveal tract and uveal melanoma, including analysis of the expression of vitamin D receptors (VDR), the activating and inactivating hydroxylases, respectively, CYP27B1 and CYP24A1, and the retinoic acid-related orphan receptors (ROR) α (RORα) and γ (RORγ) in these tissues. We further analyzed the expression of VDR, CYP27B1, CYP24A1, and ROR in relation to melanin levels, clinical stage and prognosis. Our study indicated that the uveal melanoma melanin level inversely correlated with VDR expression. We further showed that vitamin D is metabolized in uveal melanoma. This is significant because until now there has been no paper published, that would describe presence of VDR, hydroxylases CYP27B1 and CYP24A1, and RORα and RORγ in the human uveal tract and uveal melanomas. The outcomes of our research can contribute to the development of new diagnostic and therapeutic methods in uveal tract disorders, especially in uveal melanoma. The presented associations between vitamin D signaling elements and uveal melanoma in comparison to uveal tract encourage future clinical research with larger patients' population.

中文翻译：

不同黑色化水平的人葡萄膜和眼部黑色素瘤中维生素 D 受体 (VDR)、羟化酶 CYP27B1 和 CYP24A1 以及类维生素A相关孤儿受体 (ROR) 水平。

近年来，大量研究调查了维生素 D 在多种不同肿瘤中的预防作用。在本研究中，我们分析了人类葡萄膜和葡萄膜黑色素瘤中维生素 D 信号通路的各个组成部分，包括分析维生素 D 受体 (VDR) 的表达、分别激活和失活羟化酶 CYP27B1 和 CYP24A1，以及分析维生素 D 受体 (VDR) 的表达。这些组织中存在视黄酸相关孤儿受体 (ROR) α (RORα) 和 γ (RORγ)。我们进一步分析了 VDR、CYP27B1、CYP24A1 和 ROR 的表达与黑色素水平、临床分期和预后的关系。我们的研究表明葡萄膜黑色素瘤黑色素水平与 VDR 表达呈负相关。我们进一步表明维生素 D 在葡萄膜黑色素瘤中代谢。这一点很重要，因为到目前为止还没有发表论文描述人类葡萄膜和葡萄膜黑色素瘤中 VDR、羟化酶 CYP27B1 和 CYP24A1 以及 RORα 和 RORγ 的存在。我们的研究成果有助于开发葡萄膜疾病（尤其是葡萄膜黑色素瘤）的新诊断和治疗方法。与葡萄膜相比，维生素 D 信号元件与葡萄膜黑色素瘤之间的关联鼓励未来针对更多患者群体进行临床研究。

更新日期：2019-06-24

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