title: Serum miRNA signature in Moyamoya disease.
abstract: Moyamoya disease (MMD) is a cerebrovascular disease characterized by progressive stenosis of the intracranial internal carotid arteries and their proximal branches. However, the etiology of this rare disease remains unknown. Serum microRNA (miRNA) profiles have been screened to identify novel biomarkers of prognostic values. Here, we identified serum miRNAs that might play an important role in the pathogenesis of MMD. A genome-wide miRNA array analysis of two pooled serum samples from patients with MMD and controls revealed 94 differentially expressed serum miRNAs, including 50 upregulated and 44 downregulated miRNAs. In an independent MMD cohort, real-time PCR confirmed that miR-106b, miR-130a and miR-126 were significantly upregulated while miR-125a-3p was significantly downregulated in serum. GO analysis showed that the differentially expressed serum miRNAs were enriched in metabolic processes, transcription and signal transduction. Pathway analysis showed that the most enriched pathway was mTOR signaling pathway with 16 potential, functional targets. Finally, we found that 16 and 13 aberrant serum miRNAs coordinately inhibited RNF213 and BRCC3 protein expression at the posttranscriptional level, respectively, resulting in defective angiogenesis and MMD pathogenesis. To our knowledge, this is the first study to identify a serum miRNA signature in MMD. Modulation of the mechanism underlying the role of serum miRNAs in MMD is a potential therapeutic strategy and warrants further investigations.
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Dai
authors.affiliation: Department of Laboratory Medicine, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Lu
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qinghai
authors.initials: Q
authors.lastname: Huang
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Pengfei
authors.initials: P
authors.lastname: Yang
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Hong
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Wenyuan
authors.initials: W
authors.lastname: Zhao
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Li
mesh_terms: D000251:Adenosine Triphosphatases; D000328:Adult; D016022:Case-Control Studies; D000072017:Deubiquitinating Enzymes; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks; D006801:Humans; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D035683:MicroRNAs / Q000097:blood* / Q000235:genetics; D046228:Microarray Analysis; D008875:Middle Aged; D009072:Moyamoya Disease / Q000097:blood* / Q000235:genetics*; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D059467:Transcriptome; D044767:Ubiquitin-Protein Ligases / Q000235:genetics; D055815:Young Adult
chemical_list: D008565:Membrane Proteins; D035683:MicroRNAs; C557998:RNF213 protein, human; D044767:Ubiquitin-Protein Ligases; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C518017:BRCC3 protein, human; D000072017:Deubiquitinating Enzymes; D000251:Adenosine Triphosphatases
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