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从早发性家族性阿尔茨海默病患者外周血单个核细胞中进行 microRNA 分析。

Profiling microRNA from peripheral blood mononuclear cells in early-onset familial Alzheimer's disease.

机构信息

Department of Neurology.

*Daojing Li and Yanan Chen contributed equally to the writing of this article.

出版信息

Neuroreport. 2023 Feb 1;34(3):178-183. doi: 10.1097/WNR.0000000000001878. Epub 2023 Jan 20.

DOI:10.1097/WNR.0000000000001878
PMID:36719832
Abstract

MicroRNAs (miRNAs) refer to short in-length, noncoding RNAs that regulate numerous cellular functions by targeting mRNA, and numerous types of research have shown that miRNA is vitalin Alzheimer's disease. For identifying differentially expressed miRNAs in the peripheral blood mononuclear cell (PBMC) of early-onset familial Alzheimer's disease (EOFAD), we conducted this study which might give a reference for potential therapeutic targets or biomarkers for this disease. On the basis of high-throughput sequencing, we screened the miRNAs expression profiles in PBMC regarding both EOFAD patients and healthy controls, and the biological information was analyzed. Compared with the PBMC of healthy controls, 142 miRNAs were differentially expressed in EOFAD patients ( P  < 0.05), including 48 significantly differentially expressed miRNAs, 37 of which were significantly upregulated, including miR-3614-5p, miR-193A-5p, miR-2115-5p, miR-143-3p, etc. and 11 were significantly downregulated, including miR-484, miR-708-5p, miR-205-5p, miR-31-5p, etc. According to biological information analysis, 768 miRNA target genes were differentially expressed, which may be involved in multiple gene functions and cell cycle, cell senescence, and several signaling pathways, including FoxO, MAPK, Ras, mTOR, neurotrophin, etc. There are differential expressions of miRNAs in PBMC of EOFAD patients and controls, revealing their importance in Alzheimer's disease as indicated by co-expression network analysis; this may support basic information for new biomarkers or treatment exploring.

摘要

MicroRNAs (miRNAs) 是一种长度较短的非编码 RNA,通过靶向 mRNA 来调节多种细胞功能,许多类型的研究表明 miRNA 在阿尔茨海默病中至关重要。为了鉴定早发性家族性阿尔茨海默病(EOFAD)患者外周血单个核细胞(PBMC)中差异表达的 miRNA,我们进行了这项研究,这可能为该疾病的潜在治疗靶点或生物标志物提供参考。基于高通量测序,我们筛选了 EOFAD 患者和健康对照者 PBMC 中的 miRNA 表达谱,并进行了生物信息学分析。与健康对照者的 PBMC 相比,EOFAD 患者的 142 个 miRNA 表达存在差异(P<0.05),其中 48 个 miRNA 表达显著上调,包括 miR-3614-5p、miR-193A-5p、miR-2115-5p、miR-143-3p 等,11 个 miRNA 表达显著下调,包括 miR-484、miR-708-5p、miR-205-5p、miR-31-5p 等。根据生物信息学分析,有 768 个 miRNA 靶基因表达差异,这些基因可能参与多种基因功能和细胞周期、细胞衰老以及 FoxO、MAPK、Ras、mTOR、神经营养因子等多个信号通路。EOFAD 患者和对照组 PBMC 中的 miRNA 表达存在差异,通过共表达网络分析显示其在阿尔茨海默病中的重要性;这可能为新的生物标志物或治疗探索提供基础信息。

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