Small RNA sequencing of circulating small extracellular vesicles microRNAs in patients with amyotrophic lateral sclerosis

被引：17

作者：

Kim, Jin-Ah ^{[1
,2
,3
]}

Park, Canaria ^{[4
]}

Sung, Jung-Joon ^{[1
]}

Seo, Do-Jin ^{[5
]}

Choi, Seok-Jin ^{[1
]}

Hong, Yoon-Ho ^{[6
,7
]}

机构：

[1] Seoul Natl Univ Hosp, Dept Neurol, Seoul, South Korea

[2] Seoul Natl Univ, Coll Med, Dept Translat Med, Seoul, South Korea

[3] Seoul Natl Univ, Genom Med Inst, Med Res Ctr, Seoul, South Korea

[4] Harvard Med Sch, Dept Neurobiol, Boston, MA USA

[5] Chung Ang Univ, Coll Med, Dept Neurol, Seoul, South Korea

[6] Seoul Natl Univ, Coll Med, Seoul Metropolitan Govt Boramae Med Ctr, MRC,Neurosci Res Inst,Dept Neurol, Seoul, South Korea

[7] Seoul Natl Univ, Seoul Metropolitan Govt Boramae Med Ctr, Dept Neurol, 20 Boramaero 5-Gil, Seoul 07061, South Korea

来源：

SCIENTIFIC REPORTS | 2023年 / 13卷 / 01期

基金：

新加坡国家研究基金会;

关键词：

ACTIVATED PROTEIN-KINASE; CELL-CYCLE REGULATORS; MOUSE MODEL; DISEASE; BIOMARKERS; ALIGNMENT; EXOSOMES; GENES; MIRNA;

D O I：

10.1038/s41598-023-32717-y

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Dysregulation of microRNAs (miRNA) in small extracellular vesicles (sEV) such as exosomes have been implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS). Although circulating cell-free miRNA have been extensively investigated in ALS, sEV-derived miRNAs have not been systemically explored yet. Here, we performed small RNA sequencing analysis of serum sEV and identified 5 differentially expressed miRNA in a discovery cohort of 12 patients and 11 age- and sex-matched healthy controls (fold change > 2, p < 0.05). Two of them (up- and down-regulation of miR-23c and miR192-5p, respectively) were confirmed in a separate validation cohort (18 patients and 15 healthy controls) by droplet digital PCR. Bioinformatic analysis revealed that these two miRNAs interact with distinct sets of target genes and involve biological processes relevant to the pathomechanism of ALS. Our results suggest that circulating sEV from ALS patients have distinct miRNA profiles which may be potentially useful as a biomarker of the disease.

引用

页数：9

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