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烟雾病患者循环白细胞中的微小RNA表达及生物信息学分析

MicroRNA Expression in Circulating Leukocytes and Bioinformatic Analysis of Patients With Moyamoya Disease.

作者信息

Kang Kaijiang, Shen Yuan, Zhang Qian, Lu Jingjing, Ju Yi, Ji Ruijun, Li Na, Wu Jianwei, Yang Bo, Lin Jinxi, Liang Xianhong, Zhang Dong, Zhao Xingquan

机构信息

Department of Neurology, Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

China National Clinical Research Center for Neurological Diseases, Beijing, China.

出版信息

Front Genet. 2022 May 20;13:816919. doi: 10.3389/fgene.2022.816919. eCollection 2022.

Abstract

MicroRNAs (miRNAs) in exosomes had been implicated differentially expressed in patient with moyamoya disease (MMD), but the miRNAs expression in circulating leukocytes remains unclear. This study was investigated on the differential expression of miRNAs in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. A total of 30 patients with MMD and 10 healthy adults were enrolled in a stroke center from October 2017 to December 2018. The gene microarray was used to detect the differential expression profiles of miRNA in leukocytes between MMD patients and controls, and the differentially expressed miRNAs were verified by the method of real-time PCR. The Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) were used to explore the key signaling pathways and possible pathogenesis of MMD. The microarray results showed 12 differentially expressed miRNAs in leukocytes of MMD patients compared with controls (fold change >2.0, < 0.05 and FDR <0.05), of which 8 miRNAs were upregulated (miRNA-142-5p, miRNA-29b-3p, miRNA-424-5p, MiRNA-582-5p, miRNA-6807-5p, miRNA-142-3p, miRNA-340-5p, miRNA-4270), and 4 miRNAs were downregulated (miRNA-144-3p, miRNA-451a, miRNA-486-5p, miRNA-363-3p). The real-time PCR confirmed seven differentially expressed miRNAs ( < 0.05), of which 4 miRNAs (miRNA-29b-3p, miRNA-142-3p, miRNA-340-5p, miRNA-582-5p) were upregulated, and 3 miRNAs (miRNA-363-3p, miRNA-451a and miRNA-486-5p) were downregulated. Both GO and KEGG analysis suggested that the Wnt signaling pathway may be involved in the pathogenesis of MMD. In addition, miRNAs were also differentially expressed among patients with subtypes of MMD. This study indicated that miRNAs are differentially expressed in peripheral leukocytes between MMD patients and healthy adults, and among patients with subtypes of MMD. The Wnt signaling pathway is probably involved in the pathogenesis of MMD.

摘要

外泌体中的微小RNA(miRNA)已被证实在烟雾病(MMD)患者中存在差异表达,但循环白细胞中的miRNA表达仍不清楚。本研究旨在探讨MMD患者与健康成年人外周血白细胞中miRNA的差异表达,以及MMD各亚型患者之间的差异。2017年10月至2018年12月,一家卒中中心共纳入了30例MMD患者和10名健康成年人。采用基因芯片检测MMD患者与对照组白细胞中miRNA的差异表达谱,并通过实时PCR方法验证差异表达的miRNA。利用基因本体论(GO)和京都基因与基因组百科全书(KEGG)探索MMD的关键信号通路和可能的发病机制。基因芯片结果显示,与对照组相比,MMD患者白细胞中有12种差异表达的miRNA(倍数变化>2.0,P<0.05且FDR<0.05),其中8种miRNA上调(miRNA-142-5p、miRNA-29b-3p、miRNA-424-5p、MiRNA-582-5p、miRNA-6807-5p、miRNA-142-3p、miRNA-340-5p、miRNA-4270),4种miRNA下调(miRNA-144-3p、miRNA-451a、miRNA-486-5p、miRNA-363-3p)。实时PCR证实了7种差异表达的miRNA(P<0.05),其中4种miRNA(miRNA-29b-3p、miRNA-142-3p、miRNA-340-5p、miRNA-582-5p)上调,3种miRNA(miRNA-363-3p、miRNA-451a和miRNA-486-5p)下调。GO和KEGG分析均表明,Wnt信号通路可能参与MMD的发病机制。此外,MMD各亚型患者之间的miRNA也存在差异表达。本研究表明,MMD患者与健康成年人外周血白细胞中的miRNA存在差异表达,MMD各亚型患者之间也存在差异表达。Wnt信号通路可能参与MMD的发病机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e167/9163834/f4375cb4aa6b/fgene-13-816919-g001.jpg

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