Serum miRNA Signature in Moyamoya Disease

• Published in: PloS one Vol. 9; no. 8; p. e102382
• Main Authors: Dai, Dongwei, Lu, Qiong, Huang, Qinghai, Yang, Pengfei, Hong, Bo, Xu, Yi, Zhao, Wenyuan, Liu, Jianmin, Li, Qiang
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 05.08.2014; Public Library of Science (PLoS)
• Subjects: Adenosine Triphosphatases; Adult; Angiogenesis; Arteries; Bioindicators; Biology and Life Sciences; Biomarkers; Cancer therapies; Cardiovascular disease; Carotid arteries; Carotid artery; Case-Control Studies; Etiology; Female; Gene expression; Gene Expression Profiling; Gene Regulatory Networks; Genomes; Heart attacks; Hospitals; Humans; Male; Medical imaging; Medical prognosis; Medicine and Health Sciences; Membrane Proteins - genetics; Microarray Analysis; MicroRNAs; MicroRNAs - blood; MicroRNAs - genetics; Middle Aged; miRNA; Moyamoya disease; Moyamoya Disease - blood; Moyamoya Disease - genetics; Neurosurgery; NMR; Nuclear magnetic resonance; Pathogenesis; Post-transcription; Ribonucleic acid; RNA; Signal processing; Signal transduction; Signaling; Stenosis; TOR protein; TOR Serine-Threonine Kinases - genetics; TOR Serine-Threonine Kinases - metabolism; Transcriptome; Ubiquitin-Protein Ligases - genetics; Young Adult; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0102382

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.