Abstract
Single-nucleotide polymorphisms (SNPs) of microRNA (miRNA) (miRSNP) are SNPs located on miRNA genes or miRNA target sites, which have been supposed to be involved in the development of central nervous system diseases by interfering with miRNA-mediated regulatory functions. However, the association of miRSNP with post-stroke depression (PSD) has not been well-investigated. In this study, we collected 54 PSD risk genes via manual literature-mining and integrated PSD-related risk pathways based on multiple public databases. Furthermore, we systematically screened candidate functional miRSNPs for PSD and integrated a miRSNP-based PSD-associated pathway network, which included 99 miRNAs that target 12 PSD risk pathways. We also reviewed the association between three risk pathways and PSD pathogenetic mechanism thoroughly. Combining literature mining and network analysis, our results proposed an underlying mechanism of “miRSNP → miRNA → risk gene → pathway” axis effects on PSD pathogenesis, especially for rs28457673 (miR-15/16/195/424/497 family) → IGF1R → hsa04010 (MAPK signaling pathway). Our studies revealed a functional role in genetic modifier at the system level in the pathogenesis of PSD, which might provide further information for the miRSNP studies in PSD.
Highlights
Stroke is the second leading cause of mortality and has been identified as the third-most leading factor accounting for subsequent disability (Mboi et al, 2018)
Results from analyses of Gene Ontology (GO) indicated that post-stroke depression (PSD) risk-related genes were enriched significantly with respect to: inflammatory response, serotonin receptor-based signaling pathways, and apoptosis regulation (Supplementary Table 2), which coincided with already existent knowledge about the dynamics of the pathogenesis of PSD
We identified seven miRNA-associated SNPs (miRSNPs) within target sites for miRNA that might have affected the levels of expression of respective target genes and biological functions, which would further influence the status of hsa04010 (MAPK signaling pathway) in PSD
Summary
Stroke is the second leading cause of mortality and has been identified as the third-most leading factor accounting for subsequent disability (Mboi et al, 2018). Post-stroke depression (PSD) has been noted to occur in nearly 30% of survivors of stroke and is one of the most frequent complications. PSD often leads to greater incidence and degree of disability, increased recurrence of stroke, and increased mortality, Network Associated With Post-stroke Depression all of which pose significant challenges for clinicians tasked with treating patients (Hackett et al, 2005). Emerging experiments have demonstrated that genetic risk plays an important role in the dynamics underlying the progress of PSD. Many types of single-nucleotide polymorphisms (SNPs) are considered as likely role players in the dynamics and mechanistics underlying the pathogenesis of PSD (Kim et al, 2012; Zhiming Zhou et al, 2015; Liang et al, 2018), which includes SNP variants in inflammatory cytokine genes (Kim et al, 2012) and for genes in the nerve growth factor family (Liang et al, 2018). Molecular biology and genetic factors have facilitated insights into PSD; the exact mechanisms and dynamics underlying the onset, development, and progression of PSD remain unclear
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