Signature of miRNAs derived from the circulating exosomes of patients with amyotrophic lateral sclerosis.
Signature of miRNAs derived from the circulating exosomes of patients with amyotrophic lateral sclerosis.
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DOI：
10.3389/fnagi.2023.1106497
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发表时间：
2023
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
Amyotrophic lateral sclerosis (ALS) is a progressive, fatal neurodegenerative disorder (NDS) with unclear pathophysiology and few therapeutic options. Mutations in SOD1 and C9orf72 are the most common in Asian and Caucasian patients with ALS, respectively. Aberrant (microRNAs) miRNAs found in patients with gene-mutated ALS may be involved in the pathogenesis of gene-specific ALS and sporadic ALS (SALS). The aim of this study was to screen for differentially expressed miRNAs from exosomes in patients with ALS and healthy controls (HCs) and to construct a miRNA-based diagnostic model to classify patients and HCs. We compared circulating exosome-derived miRNAs of patients with ALS and HCs using the following two cohorts: a discovery cohort (three patients with SOD1-mutated ALS, three patients with C9orf72-mutated ALS, and three HCs) analyzed by microarray and a validation cohort (16 patients with gene-mutated ALS, 65 patients with SALS, and 61 HCs) confirmed by RT-qPCR. The support vector machine (SVM) model was used to help diagnose ALS using five differentially expressed miRNAs between SALS and HCs. A total of 64 differentially expressed miRNAs in patients with SOD1-mutated ALS and 128 differentially expressed miRNAs in patients with C9orf72-mutated ALS were obtained by microarray compared to HCs. Of these, 11 overlapping dysregulated miRNAs were identified in both groups. Among the 14 top-hit candidate miRNAs validated by RT-qPCR, hsa-miR-34a-3p was specifically downregulated in patients with SOD1-mutated ALS, while hsa-miR-1306-3p was downregulated in ALS patients with both SOD1 and C9orf72 mutations. In addition, hsa-miR-199a-3p and hsa-miR-30b-5p were upregulated significantly in patients with SALS, while hsa-miR-501-3p, hsa-miR-103a-2-5p, and hsa-miR-181d-5p had a trend to be upregulated. The SVM diagnostic model used five miRNAs as features to distinguish ALS from HCs in our cohort with an area under receiver operating characteristic curve (AUC) of 0.80. Our study identified aberrant miRNAs from exosomes of SALS and ALS patients with SOD1/C9orf72 mutations and provided additional evidence that aberrant miRNAs were involved in the pathogenesis of ALS regardless of the presence or absence of the gene mutation. The machine learning algorithm had high accuracy in predicting the diagnosis of ALS, shedding light on the foundation for the clinical application of blood tests in the diagnosis of ALS, and revealing the pathological mechanisms of the disease.
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影响因子：
3.7
作者：
Enderle D;Spiel A;Coticchia CM;Berghoff E;Mueller R;Schlumpberger M;Sprenger-Haussels M;Shaffer JM;Lader E;Skog J;Noerholm M
通讯作者：
Noerholm M
DOI：
10.1523/jneurosci.0558-12.2012
发表时间：
2012-06-27
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Åkerblom M;Sachdeva R;Barde I;Verp S;Gentner B;Trono D;Jakobsson J
通讯作者：
Jakobsson J
影响因子：
14.9
作者：
Cheng WC;Chung IF;Tsai CF;Huang TS;Chen CY;Wang SC;Chang TY;Sun HJ;Chao JY;Cheng CC;Wu CW;Wang HW
通讯作者：
Wang HW
影响因子：
5.1
作者：
Brennan, Samuel;Keon, Matthew;Saksena, Nitin K.
通讯作者：
Saksena, Nitin K.
散发性肌萎缩侧索硬化症白细胞中 miRNA 表达异常
影响因子：
4.8
作者：
Chen Y;Wei Q;Chen X;Li C;Cao B;Ou R;Hadano S;Shang HF
通讯作者：
Shang HF