MiR-126a-5p-Dbp and miR-31a-Crot/Mrpl4 interaction pairs crucial for the development of hypertension and stroke

Abstract

The present study aimed to integrate the mRNA and microRNA (miRNA) expression profiles of spontaneously hypertensive rats (SHR rats) and stroke-prone spontaneously hypertensive rats (SHRSP rats) to screen for potential therapeutic targets for hypertension and stroke. The datasets GSE41452, GSE31457, GSE41453 and GSE53363 were collected from the Gene Expression Omnibus (GEO) database to screen differentially expressed genes (DE Gs). The GSE53361 dataset was obtained to analyze differentially expressed miRNA s (DE Ms). The DEGs and DEMs were identified between SHR (or SHRSP) rats and normotensive Wistar-Kyoto (WKY) rats using the Linear Models for Microarray (limma) data method. Venn diagrams were used to show the SHR- specific, SHRSP-specific and SHR-SHRSP shared DEGs and DEMs, and these were utilized to construct the protein-protein interaction (PPI) and miRNA- mRNA regulatory networks. The Database for Annotation, Visualization and Integrated Discovery (DA VID) was used to explore the function of the genes. Subsequently, the connectivity Map (CMAP) database was searched to identify small-molecule drugs. Comparisons between the GSE41452-GSE31457-GSE41453 merged and GSE53363 datasets identified 2 SHR-specific, 8 SHRSP-specific and 15 SHR- SHRSP shared DE Gs. Function enrichment analysis showed that SHRSP-specific D- box binding PAR bZIP transcription factor (Dbp) was associated with circadian rhythm, and SHR- SHRSP shared carnitine O- octanoyltransferase (Crot) was involved in fatty acid metabolic processes or the inflammatory response via interacting with epoxide hydrolase 2 (EPHX2). SHR- SHRSP shared mitochondrial ribosomal protein L4 (Mrpl4) may exert roles by interacting with the threonine-tRNA ligase, TAR S2. The miRNA regulatory network predicted that upregulated Dbp could be regulated by rno-miR- 126a-5p, whereas downregulated Crot and Mrpl4 could be modulated by rno-miR- 31a. The CMAP database predicted that small-molecule drugs, including botulin, Gly-His-L ys, and podophyllotoxin, may possess therapeutic potential. In conclusion, the present study has identified Dbp, Crot and Mrpl4 as potential targets for the treatment of hypertension and stroke. Furthermore, the expression of these genes may be reversed by the above miRNA s or drugs.