Identification of Potential Hub Genes in Alopecia Areata

IF 3.5 3区 医学 Q1 DERMATOLOGY
Runqiu Liu, Longdan Liu, Jiandan Xu, Xiaoting Wen, Yannan Jiang, Qi Qi, Jie Qin, Pingping Qin
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Abstract

Alopecia areata (AA) is an immune-mediated chronic alopecia disease, but its specific pathogenesis is unclear. Gene expression data for AA patients (AAs) and healthy controls (HCs) were retrieved from the GEO database, and the differentially expressed genes (DEGs) between AAs and HCs were identified. Then, GO, KEGG and GSEA analysis were performed. A PPI network for the DEGs was then constructed to screen for hub genes, which were validated by three additional datasets. Subsequently, the potential miRNAs interacting with the hub genes were obtained through TarBase and miRNet. The differentially expressed lncRNAs (DElncRs) were obtained for subcellular localisation analysis, and the DElncRs located in the cytoplasm were further screened to identify miRNAs that interact with them. The shared miRNAs interacting with the hub genes and lncRNAs were used to construct a network of mRNA-miRNA-lncRNA interactions. Lastly, ROC analysis was performed to evaluate the potential diagnostic value of the hub genes and DElncRs identified. A total of 173 DEGs were obtained, mainly enriched in cytokines, chemokines, hair follicle development and hair cycle related signalling pathways. Through PPI screening and validation based on 3 additional datasets, 24 hub genes were finally yielded. Of them, five hub genes were upregulated and the potential miRNAs that interact with these five hub genes were identified. Additionally, 26 DElncRs were obtained, including 9 upregulated lncRNAs located in the cytoplasm that were predicted to interact with the miRNAs. Finally, an mRNA-miRNA-lncRNA regulatory network was constructed using five hub genes, four lncRNAs and their shared five miRNAs. The regulatory relationship between CD8A, mir-185-5p and FOXD2-AS1 might be crucial in AA pathogenesis, with CD8A and FOXD2-AS1 exhibiting diagnostic potential. CD8A and FOXD2-AS1 may serve as potential therapeutic targets in AA.

确定脱发症的潜在枢纽基因
斑秃(AA)是一种免疫介导的慢性脱发疾病,但其具体发病机制尚不清楚。研究人员从 GEO 数据库中检索了 AA 患者(AAs)和健康对照(HCs)的基因表达数据,并确定了 AAs 和 HCs 之间的差异表达基因(DEGs)。然后进行了 GO、KEGG 和 GSEA 分析。然后构建了 DEGs 的 PPI 网络,以筛选枢纽基因,并通过另外三个数据集进行验证。随后,通过 TarBase 和 miRNet 获得了与枢纽基因相互作用的潜在 miRNA。对差异表达的 lncRNA(DElncRs)进行亚细胞定位分析,并进一步筛选位于细胞质中的 DElncRs,以确定与其相互作用的 miRNA。与枢纽基因和lncRNA相互作用的共有miRNA被用来构建mRNA-miRNA-lncRNA相互作用网络。最后,进行了 ROC 分析,以评估所发现的中心基因和 DElncRs 的潜在诊断价值。结果共发现了 173 个 DEGs,主要富集在细胞因子、趋化因子、毛囊发育和毛发周期相关信号通路中。通过基于另外 3 个数据集的 PPI 筛选和验证,最终得到了 24 个中心基因。其中,5 个中枢基因上调,与这 5 个中枢基因相互作用的潜在 miRNAs 也被鉴定出来。此外,还得到了 26 个 DElncRs,包括 9 个位于细胞质的上调 lncRNA,预测这些 lncRNA 可与 miRNA 相互作用。最后,利用五个中心基因、四个lncRNA和它们共有的五个miRNA构建了一个mRNA-miRNA-lncRNA调控网络。CD8A、mir-185-5p和FOXD2-AS1之间的调控关系可能在AA发病机制中至关重要,其中CD8A和FOXD2-AS1具有诊断潜力。CD8A和FOXD2-AS1可能是AA的潜在治疗靶点。
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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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