与维生素 D 受体信号有关的基因转录组分析揭示了皮肤癌之间的差异。

IF 3.5 3区 医学 Q1 DERMATOLOGY Experimental Dermatology Pub Date : 2024-10-22 DOI:10.1111/exd.15160
Juliana Polizel Ocanha-Xavier, José Cândido Caldeira Xavier-Junior Jr, Hélio Amante Miot, Márcia Guimarães da Silva, Mariângela Esther Alencar Marques
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引用次数: 0

摘要

维生素 D 能激活维生素 D 受体(VDR),VDR 优先与视黄醇 X 受体-α(RXRα)二聚化。这种异源二聚体与对维生素 D 有反应的基因元件相连,抑制或刺激基因活性。我们对 VDR/RXRα 进行了 Nanostring® 分析,以比较非黑色素瘤皮肤癌(基底细胞癌 (BCC) 和鳞状细胞癌 (SCC))和黑色素细胞病变(皮内痣 (IN) 和黑色素瘤 (MM))与对照皮肤中这种异源二聚体的 mRNA 表达及其相关转录组。为了评估 BCC、SCC、IN 和 MM 中的 VDR、RXRα 和其他 22 个相关基因,使用 Nanostring®(一种可进行多种 mRNA 分析的平台)分析了石蜡样本的转录组。共有 46 个样本,包括 11 个 BCC、10 个 SCC、10 个 IN、12 个 MM 和 3 组对照皮肤。大多数 mRNA 在病变组和对照组之间存在差异。BCC和SCC的NCOR2上调;MM和IN的RXRγ高于对照组。与对照组相比,BCC 组的 TP53、FOXO3 和 MED1 有显著差异。黑色素瘤和皮内痣仅在 AhR 方面存在差异。所有组的 VDR 和 RXRα 均低于对照组。面板显示,非黑素细胞癌症之间存在明显差异,而黑素细胞病变之间则略有不同。研究维生素 D 通过其受体和 RXRα 产生的影响是一个令人兴奋的问题,有助于了解这一途径的重要性。
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Transcriptomic analysis of genes associated with vitamin D receptor signalling reveals differences between skin cancers

Vitamin D activates the vitamin D receptor (VDR), which dimerizes preferentially with the retinoid X receptor-α (RXRα). This heterodimer connects with genetic elements responsive to vitamin D, inhibiting or stimulating gene activity. We performed Nanostring® analysis of VDR/RXRα to compare the mRNA expression of this heterodimer and their correlated transcriptomes in non-melanoma skin cancer (basal cell carcinomas (BCC) and squamous cell carcinomas (SCC)) and melanocytic lesions (intradermal nevi (IN), and melanomas (MM)) with control skin. To evaluate VDR, RXRα and other 22 correlated genes in BCC, SCC, IN and MM, paraffin samples had their transcriptomes analysed using Nanostring®, a platform that allows multiple mRNA analyses. There were 46 samples, including 11 BCC, 10 SCC, 10 IN, 12 MM and 3 pools of control skins. Most mRNAs differed between the lesion groups and the control group. BCC and SCC NCOR2 were upregulated; in MM and IN, RXRγ was higher than in the control group. TP53, FOXO3 and MED1 showed a significant difference when we compared the BCC group to the SCC group. Melanoma and intradermal nevi differed only in AhR. VDR and RXRα were lower than the control in all groups. The panel shows a clear difference between the non-melanocytic cancers and, on the other hand, a slight difference between the melanocytic lesions. The study of vitamin D's influence through its receptor and RXRα is an exciting issue for understanding the importance of this pathway, and the present study can impact the prevention and treatment strategies, mainly in non-melanocytic tumours.

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来源期刊
Experimental Dermatology
Experimental Dermatology 医学-皮肤病学
CiteScore
6.70
自引率
5.60%
发文量
201
审稿时长
2 months
期刊介绍: Experimental Dermatology provides a vehicle for the rapid publication of innovative and definitive reports, letters to the editor and review articles covering all aspects of experimental dermatology. Preference is given to papers of immediate importance to other investigators, either by virtue of their new methodology, experimental data or new ideas. The essential criteria for publication are clarity, experimental soundness and novelty. Letters to the editor related to published reports may also be accepted, provided that they are short and scientifically relevant to the reports mentioned, in order to provide a continuing forum for discussion. Review articles represent a state-of-the-art overview and are invited by the editors.
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