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鉴定 UVB 照射后人皮肤中的潜在免疫相关 ceRNA 调控网络。

Identification of potential immune-related ceRNA Regulatory Network in UVB-irradiated human skin.

机构信息

Department of Dermatology, The Second Affiliated Hospital of Nanjing Medical University, Nanjing, China.

出版信息

Biotechnol Genet Eng Rev. 2023 Oct;39(2):1297-1320. doi: 10.1080/02648725.2023.2175501. Epub 2023 Feb 9.

Abstract

For a better understanding the molecular biomarkers in UVB-induced skin damage, and its potential mechanism, we downloaded two microarray data sets on skin UVB damage from the Gene Expression Omnibus (GEO): GSE21429, GSE56754. By using the Limma package to analyze differential gene expression and co-expression network analysis to screen module genes, 16 common genes were identified (16 up-regulated). Gene Ontology analysis to explore the functional roles of these genes indicated that the common genes were associated mainly with melanin biosynthetic process and metabolic process. Gene Set Enrichment Analysis provided evidence that the most gene sets enriched in immune and inflammation-related signaling pathways in the UVB-treated subjects, as compared with the untreated subjects. The PPI network genes were ranked according to the degree of connectivity, the top three ranked genes: "MLANA", "GPR143" and "SFTPC" were identified as potential biomarkers using the area under the receiver operating characteristic curve. The relative proportion of 22 immune cell types was then calculated by using the CIBERSORT algorithm. A higher follicular helper T cell ratio in UVB-treated samples compared to untreated samples was observed. Moreover, three hub genes have also been shown to be associated with immune cells. Finally, through multiple online miRNA databases, we propose MLANA-miR-573-MALAT1/NEAT1, GPR143-miR-138-5p-MALAT1/ KCNQ1OT1 might be potential RNA regulatory pathways that control disease progression in UVB-induced skin damage. In summary, the present results provide novel insights into the UVB-radiation related biological process changes, and further offer a new clinical application for prognosis and diagnostic prediction of UVB radiation-mediated skin damage.

摘要

为了更好地理解 UVB 诱导的皮肤损伤中的分子生物标志物及其潜在机制,我们从基因表达综合数据库(GEO)下载了两个关于皮肤 UVB 损伤的微阵列数据集:GSE21429、GSE56754。通过使用 Limma 包分析差异基因表达和共表达网络分析筛选模块基因,鉴定出 16 个共同基因(16 个上调)。GO 分析探讨这些基因的功能作用表明,共同基因主要与黑色素生物合成过程和代谢过程相关。基因集富集分析提供了证据,表明与未经处理的受试者相比,UVB 处理的受试者中富集的基因集主要与免疫和炎症相关信号通路有关。根据连通度对 PPI 网络基因进行排序,排名前三位的基因:“MLANA”、“GPR143”和“SFTPC”,使用受试者工作特征曲线下面积被鉴定为潜在的生物标志物。然后使用 CIBERSORT 算法计算 22 种免疫细胞类型的相对比例。与未处理的样本相比,在 UVB 处理的样本中观察到滤泡辅助 T 细胞比例更高。此外,三个枢纽基因也与免疫细胞有关。最后,通过多个在线 miRNA 数据库,我们提出 MLANA-miR-573-MALAT1/NEAT1、GPR143-miR-138-5p-MALAT1/KCNQ1OT1 可能是控制 UVB 诱导的皮肤损伤疾病进展的潜在 RNA 调控途径。总之,本研究结果为 UVB 辐射相关生物学过程变化提供了新的见解,并为 UVB 辐射介导的皮肤损伤的预后和诊断预测提供了新的临床应用。

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