Yang Hedan, Li Xiuzhen, Zhang Xiaoli, Ge Yiping, Yang Yin, Lin Tong
Department of Cosmetic Laser Surgery, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, People's Republic of China.
Jiangsu Key Laboratory of Molecular Biology for Skin Diseases and STIs, Hospital of Dermatology, Chinese Academy of Medical Sciences and Peking Union Medical College, Nanjing, 210042, People's Republic of China.
Clin Cosmet Investig Dermatol. 2025 Aug 30;18:2067-2077. doi: 10.2147/CCID.S528604. eCollection 2025.
Vitiligo is an acquired depigmentary disorder caused by the loss of functional melanocytes. Increasing evidence suggests that competing endogenous RNA (ceRNA) interactions participate in this process, yet their global architecture in vitiligo remains unclear.
To delineate a long non-coding RNA (lncRNA)-microRNA (miRNA)-mRNA ceRNA network associated with vitiligo and to identify blood-borne RNA markers with diagnostic potential.
miRNA, mRNA, and lncRNA expression data from vitiligo patients and healthy controls were obtained from the GEO database (GSE141655 and GSE186928). Differentially expressed (DE) mRNAs, miRNAs and lncRNAs were screened (|log FC| > 0.5, adj. < 0.05). Functional enrichment, STRING-based protein-protein interaction (PPI) mapping, and lncRNA-mRNA co-expression analysis (Pearson r > 0.9) was performed. miRNA-mRNA pairs were predicted with miRWalk 3.0, and miRNA-lncRNA pairs with miRanda v3.3a (score ≥ 140, energy ≤-20 kcal mol¹). Triplets that shared the same miRNA, displayed positive lncRNA--mRNA correlation, and showed inverse expression relative to the miRNA were combined into a ceRNA network; hub nodes were ranked by degree centrality. Candidate lncRNAs were validated by RT-qPCR in peripheral blood from 20 vitiligo patients and 20 matched controls.
A total of 454 DE-mRNAs (341 down-, 113 up-regulated), 22 DE-miRNAs (6 down-, 16 up-regulated), and 281 DE-lncRNAs (112 down-, 169 up-regulated) were identified. Enrichment analysis highlighted pathways linked to melanogenesis, oxidative stress, PI3K-Akt, JAK-STAT and IL-17 signalling. The ceRNA network comprised 33 lncRNAs, 12 miRNAs and 58 mRNAs; SLC32A1, GRIA2, PRKACG and WNT1 were top hub proteins in the PPI sub-network. Blood validation confirmed up-regulation of CASC19, NUCB1-AS1 and LINC01485 and down-regulation of VAV3-AS1, SPATA13-AS1, ZNF350-AS1 and LINC00677 (all < 0.05).
Our findings map a vitiligo-related ceRNA landscape and pinpoints seven circulating lncRNAs with diagnostic promise. The results provide a foundation for probing non-coding RNA-mediated mechanisms and developing targeted therapies for vitiligo.
白癜风是一种由功能性黑素细胞缺失引起的获得性色素脱失性疾病。越来越多的证据表明，竞争性内源RNA（ceRNA）相互作用参与了这一过程，但其在白癜风中的整体结构仍不清楚。
描绘与白癜风相关的长链非编码RNA（lncRNA）-微小RNA（miRNA）-信使RNA（mRNA）ceRNA网络，并鉴定具有诊断潜力的血液borne RNA标志物。
从GEO数据库（GSE141655和GSE186928）获取白癜风患者和健康对照的miRNA、mRNA和lncRNA表达数据。筛选差异表达（DE）的mRNA、miRNA和lncRNA（|log FC|>0.5，校正P值<0.05）。进行功能富集、基于STRING的蛋白质-蛋白质相互作用（PPI）图谱分析和lncRNA-mRNA共表达分析（Pearson相关系数r>0.9）。用miRWalk 3.0预测miRNA-mRNA对，用miRanda v3.3a预测miRNA-lncRNA对（得分≥140，能量≤-20 kcal mol-1）。将共享相同miRNA、显示lncRNA-mRNA正相关且相对于miRNA呈反向表达的三联体组合成ceRNA网络；通过度中心性对枢纽节点进行排名。通过RT-qPCR在20例白癜风患者和20例匹配对照的外周血中验证候选lncRNA。
共鉴定出454个DE-mRNA（341个下调，113个上调）、22个DE-miRNA（6个下调，16个上调）和281个DE-lncRNA（112个下调，169个上调）。富集分析突出了与黑素生成、氧化应激、PI3K-Akt、JAK-STAT和IL-17信号通路相关的途径。ceRNA网络由33个lncRNA、12个miRNA和58个mRNA组成；SLC32A1、GRIA2、PRKACG和WNT1是PPI子网中的顶级枢纽蛋白。血液验证证实CASC19、NUCB1-AS1和LINC01485上调，VAV3-AS1、SPATA13-AS1、ZNF350-AS1和LINC00677下调（均P<0.05）。
我们的研究结果描绘了与白癜风相关的ceRNA图谱，并确定了7种具有诊断前景的循环lncRNA。这些结果为探索非编码RNA介导的机制和开发白癜风的靶向治疗提供了基础。
