Long Noncoding RNAs and Their Regulatory Network: Potential Therapeutic Targets for Adult Moyamoya Disease.
OBJECTIVE
To investigate long noncoding ribonucleic acid (lncRNA) expression patterns in adult moyamoya disease (MMD) patients and explore their possible roles in the pathophysiology of MMD.


METHODS
A healthy control group (n = 10) and an MMD group (n = 15) were evaluated. RNA was extracted from peripheral blood samples and hybridized to microarray to get lncRNA expression profiles. Then predicted lncRNA target genes were identified, and bioinformatics analysis was performed to investigate their molecular functions.


RESULTS
In the MMD group, 3649 lncRNAs exhibited more than 2-fold expression than their counterparts in the healthy control group; of these, 1494 were upregulated, while 2155 were downregulated. Principal component analysis and Hclust analysis produced completely different clusters between the 2 groups. Gene ontology and KEGG pathway enrichment analysis suggested that the differentially expressed lncRNAs regulate multiple signaling pathways that were related with inflammation and vascular disease, and mitogen-activated protein kinase (MAPK) signaling pathway was the core regulatory pathway.


CONCLUSIONS
Long noncoding RNA expression profiles were quite different between MMD and control groups. Multiple signaling pathways that were closely associated with immune response, vasculogenesis, and smooth muscle contraction were indicated to participate in lncRNAs regulatory mechanism; of these, MAPK signaling pathway, which has been well studied for the treatment of many other cardiovascular diseases, was the core of this regulatory network. Our findings could help further understand the pathophysiology of MMD and provide new potential therapeutic targets.
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China; China National Clinical Research Center for Neurological Diseases, Beijing, P. R. China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, P. R. China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, P. R. China.
Faliang
F
Gao
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China; China National Clinical Research Center for Neurological Diseases, Beijing, P. R. China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, P. R. China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, P. R. China.
Lanbing
L
Yu
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China; China National Clinical Research Center for Neurological Diseases, Beijing, P. R. China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, P. R. China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, P. R. China.
Dong
D
Zhang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China; China National Clinical Research Center for Neurological Diseases, Beijing, P. R. China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, P. R. China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, P. R. China.
Yan
Y
Zhang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China; China National Clinical Research Center for Neurological Diseases, Beijing, P. R. China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, P. R. China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, P. R. China.
Rong
R
Wang
Department of Neurosurgery, Beijing Tiantan Hospital, Capital Medical University, Beijing, P. R. China; China National Clinical Research Center for Neurological Diseases, Beijing, P. R. China; Center of Stroke, Beijing Institute for Brain Disorders, Beijing, P. R. China; Beijing Key Laboratory of Translational Medicine for Cerebrovascular Diseases, Beijing, P. R. China. Electronic address: zhaojz205@163.com.
Jizong
J
Zhao
D000328:Adult; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics; D005819:Genetic Markers / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods; D006801:Humans; D020935:MAP Kinase Signaling System / Q000235:genetics*; D008297:Male; D058990:Molecular Targeted Therapy / Q000379:methods; D009072:Moyamoya Disease / Q000097:blood* / Q000235:genetics*; D005810:Multigene Family / Q000235:genetics; D062085:RNA, Long Noncoding / Q000097:blood* / Q000235:genetics*
D005819:Genetic Markers; D062085:RNA, Long Noncoding
Long noncoding RNA; MAPK signaling pathway; Moyamoya disease; Stroke; Vascular disease