Differential expression of circular RNAs of MVP, RGS9 and DLGAP4 genes in the frontal cortex of ischemic rats

The aim. Determination of changes in the levels of circular RNAs (circRNAs) of the Mvp, Rgs9 and Dlgap4 genes in the frontal cortex of ischemic rats 24 h after transient occlusion of the right middle cerebral artery (tMCAO). CircRNAs are covalently closed biogenic RNA molecules that have increased metabolic stability, the ability to participate in the regulation of gene expression and act as potential biomarkers of diseases and therapeutic targets for treatment. Previously, we demonstrated the involvement of genes of the neurosignaling and inflammatory systems in the response to ischemic injury, and also revealed significant changes in the expression of circRNA of Rgs9 and Mvp genes in subcortical brain structures 24 hours after tMCAO in rats. These genes encode proteins involved in the inflammatory response (Mvp) and nerve signal transmission (Rgs9). Here, the circRNA of the Mvp and Rgs9 genes were analyzed. Additionally, the circRNA of the Dlgap4 gene, which has been shown to play a role in ischemic stroke, was analyzed too. Materials and methods. Wistar rats, rat tMCAO model, real-time PCR, bioinformatics. Results. Changes in the levels of circRNAs of the Mvp, Rgs9, and Dlgap4 genes were studied in the frontal cortex, which contains predominantly regenerative penumbra cells, 24 h after tMCAO. We found that the circRNA of the Mvp gene demonstrated reliable increases in expression levels (fold change >1.5; P<0.05) in groups of ischemic rats relative to sham-operated animals, while the change in the level of circRNA of the Rgs9 and Dlgap4 genes was insignificant. Using bioinformatics, probable binding sites for microRNAs capable of controlling the work of genes of focal adhesion systems, neurotransmission and neurogenesis were identified in the circRNA sequences of the Dlgap4, Mvp and Rgs9 genes. Conclusion. The results allow us to assess the significance of circRNAs of Mvp, Rgs9 and Dlgap4 genes for the possibility of further creating promising diagnostic systems and choosing stroke treatment tactics on their basis.