PRJNA793196
Integrative analysis of peripheral blood mononuclear cell miRNA and mRNA in coronary heart disease patients
The aim of this study was to explore the differences in microRNA (miRNA) and mRNA (messenger RNA) profiles in peripheral blood mononuclear cells (PBMCs) between coronary heart disease (CHD) patients with and health control and to assess the values of differentially expressed miRNAs (DEMs) regarding CHD risk and research specific miRNA function in CHD.Methods:Six CHD patients and eight age- and gender-matched Health control were enrolled in the RNA-seq research stage.30 CHD and pairs of health control were enrolled in the validation stage. Peripheral blood samples were collected from all the participants, and PBMCs were separated for miRNA and mRNA detection. RNA-sequencing and quantitative polymerase chain reactions were performed to assess the miRNA and mRNA expression. The dual-luciferase report experiment and Western blot were used to verify the interaction of miRNA its potential target genes.Results:In the explore research stage, Differential expression analysis showed that CHD patients could be distinguished from health control using PMBC miRNA and mRNA expressions profile; 26 downregulated DEMs and 32 upregulated DEMs in PBMCs were identified in CHD patients using volcano map(|log2FC|>1.5 and P-value < 0.05). 87 downregulated DEGs and 152 upregulated DEGs in PBMCs were identified in CHD patients using a volcano map. In the validation stage, Three miRNAs include miR-130a-5p, miR-34a-5p, and miR-150-5p were found to be markedly dysregulated in CHD patients.miR-34a-5p is up repression and FOSL1 is down-regulated in HUVEC and CHD patients. co-expression analysis shows mir-34a-5p targets participate in cell adhesion and the Integrin signaling pathway. Bioinformatic prediction revealed that miR-34a putatively binds to the 3'-UTR of the FOSL1 gene and the Dual-Luciferase Reporter assay confirms it. Overexpression of miR-34a-5p promoted HUVEC cell proliferation and adhesion, whereas knockdown of miR-34a-5p showed the opposite effects. Furthermore, miR-34a overexpression to activation of the integrin signaling pathway in HUVEC cells.Conclusion:CHD patients could be differentiated according to PBMC miRNA profiles, and the miR-130a-5p, miR-34a-5p, miR-150-5p, and FOSL1 was potentially biomarker in CHD diagnosis.miR-34a regulates FOSL1 expression to promote proliferation and adhesion in HUVEC cells via the integrin signaling pathway.