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探索儿童非感染性葡萄膜炎中的微小RNA特征:患者样本的荟萃分析和分子谱分析

Exploring microRNA signatures in pediatric non-infectious uveitis: meta-analysis and molecular profiling of patient samples.

作者信息

Wawrzyniak Olga, Wawrzyniak Dariusz, Smuszkiewicz Michał, Głodowicz Paweł, Gotz-Więckowska Anna, Rolle Katarzyna

机构信息

Department of Ophthalmology, Poznan University of Medical Sciences, Augustyna Szamarzewskiego 84, 61-848, Poznan, Poland.

Department of Molecular Neurooncology, Institute of Bioorganic Chemistry Polish Academy of Sciences, Zygmunta Noskowskiego 12/14, 61-704, Poznan, Poland.

出版信息

J Appl Genet. 2024 Dec 19. doi: 10.1007/s13353-024-00922-8.

Abstract

To find a distinct non-coding RNA characteristic for idiopathic uveitis in the pediatric population. To explore the autoimmune-related miRNA expression profile in pediatric patients with idiopathic uveitis (IU) and juvenile idiopathic arthritis-associated uveitis (JIA-AU) and find a common molecular background for idiopathic uveitis and other autoimmune diseases. The expression levels of miRNAs were analyzed by quantitative real-time PCR using serum samples from patients with idiopathic uveitis (n = 8), juvenile idiopathic arthritis-associated uveitis (n = 7), and healthy controls. We selected the most promising miRNAs from the original research papers: miR-16-5p, miR-26a-5p, miR-145-5p, and miR-451a as markers for juvenile idiopathic arthritis; miR-23a-3p, miR-29a-3p, miR-140-5p, miR-193a-5p, and miR-491-5p for uveitis in the adult population; and miR-125a-5p, miR-146a-5p, miR-155-5p, miR-223-5p, and miR-223-3p characteristic for both diseases and confirm their expression changes in serum from children with idiopathic uveitis. We comprehensively reviewed the literature enrolling the papers that met the inclusion criteria (miRNA and non-infectious uveitis/juvenile idiopathic arthritis) and performed target prediction analysis of appoint miRNAs. It additionally confirmed that altered miRNAs target the immunologically involved genes. Immunological-involved miRNAs such as miR-146a-5p and miR-155-5p show diverse expression levels in different patients as they interact with multiple targets. miR-204-5p is downregulated in both patient groups compared to healthy controls. miR-204-5p and miR-155-5p are candidates for molecular markers of autoimmune uveitis. We did not identify the miRNAs specific only to idiopathic uveitis, but for the first time in the pediatric population, we confirmed that this disease entity shares a molecular basis with other autoimmune diseases. Further studies are required to elucidate the molecular interactions among miRNAs, cytokines, and transcription factors within the intricate immune response, particularly in the eye.

摘要

寻找小儿特发性葡萄膜炎独特的非编码RNA特征。探索小儿特发性葡萄膜炎(IU)和青少年特发性关节炎相关性葡萄膜炎(JIA - AU)患者中与自身免疫相关的miRNA表达谱,为特发性葡萄膜炎及其他自身免疫性疾病寻找共同的分子背景。使用特发性葡萄膜炎患者(n = 8)、青少年特发性关节炎相关性葡萄膜炎患者(n = 7)及健康对照者的血清样本,通过定量实时PCR分析miRNA的表达水平。我们从原始研究论文中挑选出最具潜力的miRNA:将miR - 16 - 5p、miR - 26a - 5p、miR - 145 - 5p和miR - 451a作为青少年特发性关节炎的标志物;将miR - 23a - 3p、miR - 29a - 3p、miR - 140 - 5p、miR - 193a - 5p和miR - 491 - 5p作为成人葡萄膜炎的标志物;将miR - 125a - 5p、miR - 146a - 5p、miR - 155 - 5p、miR - 223 - 5p和miR - 223 - 3p作为两种疾病的特征性标志物,并证实它们在特发性葡萄膜炎患儿血清中的表达变化。我们全面回顾了纳入符合纳入标准(miRNA与非感染性葡萄膜炎/青少年特发性关节炎)论文的文献,并对指定的miRNA进行了靶标预测分析。这进一步证实了改变的miRNA靶向免疫相关基因。免疫相关的miRNA,如miR - 146a - 5p和miR - 155 - 5p,由于它们与多个靶标相互作用,在不同患者中表现出不同的表达水平。与健康对照相比,miR - 204 - 5p在两组患者中均下调。miR - 204 - 5p和miR - 155 - 5p是自身免疫性葡萄膜炎分子标志物的候选者。我们未鉴定出仅特发性葡萄膜炎特有的miRNA,但首次在小儿群体中证实该疾病实体与其他自身免疫性疾病共享分子基础。需要进一步研究以阐明复杂免疫反应中,特别是在眼部,miRNA、细胞因子和转录因子之间的分子相互作用。

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