Author:
Yang Ziqi,Wang Ruonan,Chen Xingyu,Zhao Dexi
Abstract
This study aimed to further explore the underlying molecular mechanism of intracerebral hemorrhage (ICH), gene expression
profile GSE24265, containing perihematomal tissues, contralateral grey matter, and contralateral white matter was retrieved
and analyzed. The data was hierarchically clustered and the differentially expressed genes (DEGs) were screened. Functional
analysis and protein interaction analysis of DEG hubs were performed, and the miRNA‑transcription factor (TF)‑target
network was built. In addition, the candidate small-molecule compounds that might reverse the expression of an ICH‑linked
gene were identified by CMap. This method revealed a total of 408 DEGs. Five modules including chemokine-related, antigen
immune-related, pathogen infection, cell reaction, and positive regulation of tyrosine phosphorylation and MAPK cascade
were identified. The expression levels of CCL5, CXCL8, ICAM1, IL-1B, IL-6, VCAM1, and VEGFA were correlated with ICH among
the top 10 hub genes obtained in the protein protein interaction (PPI) network. A total of 237 miRNA‑TF‑target regulatory
relationships were obtained, including 6 TFs, 11 miRNAs and 105 target genes. Finally, the CMap database identified
Prestwick-1083, xamoterol, ifosfamide, methyldopate, nifurtimox, propranolol, and methoxamine as potential therapeutic
agents for ICH while doxorubicin, menadione and azacitidine may increase its pathogenicity. Furthermore, CCL5, CXCL8 and
VEGFA may be novel candidate susceptibility genes for ICH. Some small-molecule drugs, including xamoterol may be used
for the treatment of ICH.
Publisher
The Nencki Institute of Experimental Biology, Polish Academy of Sciences
Subject
General Medicine,General Neuroscience
Cited by
2 articles.
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