Abstract
In recent years, more and more studies focus on the roles of genes or miRNAs in stroke. However, the molecular mechanism connecting miRNAs and their targetgenes remains unclear. The aim of this study was to determine the differential regulation and correlations between miRNAs and their targetgenes in human stroke. Stroke-related miRNAs were obtained from the Human MicroRNA Disease Database (HMDD) and their targetgenes were generated from three independent sources. Kappa score was used to create the network and the functional modules. A total of 11 stroke-related miRNAs were identified from the HMDD and 441 overlapping targetgenes were extracted from the three databases. By network construction and GO analysis, 13 functional modules, 186 biological processes, and 21 pathways were found in the network, of which functional module 8 was the largest module, cellular-related process and phosphate-related process were the most important biological processes, and MAPK signaling pathway was the most significant pathway. In our study, all miRNAs regulate the stroke modular network by their targetgenes. After the validation of miRNAs, we found that miR-605 and miR-181d were highly expressed in the blood of stroke patients which never reported before may supply novel target for treatment.
Highlights
Stroke is the third leading cause of death and long-term disability worldwide
One study found that several miRNAs were differentially expressed in blood cells of patients with acute ischemic stroke, and these miRNAs were predicted to regulate several genes in pathways previously identified by gene expression analyses[6]
We aim to identify stroke-related miRNAs and their targetgenes, and construct a miRNA-targetgenes functional network to find out important biological processes and determine which miRNAs
Summary
Stroke is the third leading cause of death and long-term disability worldwide. The complexity of the disease resulting from its multiple underlying risk factors has impeded both diagnosis and potential therapy. Another study constructed a miRNA-miRNA network using predicted targetgenes of mouse miRNAs microarray expression profiles data to investigate the complex synergistic relationships between miRNAs, identify potential miRNA or targetgenes, and search out the associated biological processes[7]. These studies have partially revealed the functions of miRNAs and targetgenes in stroke. There is a lack of studies that can fully reveal the roles of biological processes, genes, and miRNAs in human stroke miRNAs network. These analyses may provide a theoretical basis for further studies and help to uncover the complex mechanisms underlying stroke
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