Author/Authors :
Gu, Xuefeng Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital - Shanghai, China , Jiang, Dongyang Department of Cardiology - Pan-Vascular Medicine Institute - Shanghai Tenth People’s Hospital - Tongji University School of Medicine - Shanghai, China , Yang, Yue Department of Pathology - Hongqi Hospital Affiliated to Mudanjiang Medical University - Mudanjiang, China , Zhang, Peng School of Clinical Medicine - Shanghai University of Medicine & Health Sciences - Shanghai, China , Wan, Guoqing Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital - Shanghai, China , Gu, Wangxian Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital - Shanghai, China , Shi, Junfeng Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital - Shanghai, China , Jiang, Liying Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital - Shanghai, China , Chen, Bing Department of Neurosurgery - Affiliated Hospital of Guangdong Medical University - Zhanjiang - Guangdong, China , Zheng, Yanjun Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital - Shanghai, China , Liu, Dingsheng Department of Oncology and Hematology - Shanghai University of Medicine & Health Sciences Affiliated Zhoupu Hospital, China , Guo, Sufen Department of Pathology - Hongqi Hospital Affiliated to Mudanjiang Medical University - Mudanjiang, China , Lu, Changlian Shanghai University of Medicine & Health Science Affiliated Zhoupu Hospital - Shanghai, China
Abstract :
Moyamoya disease (MMD) is a rare cerebrovascular disease characterized by chronic progressive stenosis or occlusion
of the bilateral internal carotid artery (ICA), the anterior cerebral artery (ACA), and the middle cerebral artery (MCA). MMD is
secondary to the formation of an abnormal vascular network at the base of the skull. However, the etiology and pathogenesis of
MMD remain poorly understood. Methods. A competing endogenous RNA (ceRNA) network was constructed by analyzing
sample-matched messenger RNA (mRNA), long non-coding RNA (lncRNA), and microRNA (miRNA) expression profiles from
MMD patients and control samples. Then, a protein-protein interaction (PPI) network was constructed to identify crucial genes
associated with MMD. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes pathway (KEGG) enrichment
analyses were employed with the DAVID database to investigate the underlying functions of differentially expressed mRNAs
(DEmRNAs) involved in the ceRNA network. CMap was used to identify potential small drug molecules. Results. A total of 94
miRNAs, 3649 lncRNAs, and 2294 mRNAs were differentially expressed between MMD patients and control samples. A
synergistic ceRNA lncRNA-miRNA-mRNA regulatory network was constructed. Core regulatory miRNAs (miR-107 and miR423-5p) and key mRNAs (STAT5B, FOSL2, CEBPB, and CXCL16) involved in the ceRNA network were identified. GO and
KEGG analyses indicated that the DEmRNAs were involved in the regulation of the immune system and inflammation in
MMD. Finally, two potential small molecule drugs, CAY-10415 and indirubin, were identified by CMap as candidate drugs for
treating MMD. Conclusions. The present study used bioinformatics analysis of candidate RNAs to identify a series of clearly
altered miRNAs, lncRNAs, and mRNAs involved in MMD. Furthermore, a ceRNA lncRNA-miRNA-mRNA regulatory network
was constructed, which provides insights into the novel molecular pathogenesis of MMD, thus giving promising clues for
clinical therapy.
Keywords :
RNA , RNA-Associated , MMD , Moyamoya
