Mechanism of hsa-miR-423-5p activating IL1R1 gene in coronary heart disease
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Abstract
Objective:To analyze the mechanism of hsa-miR-423-5p target genes in coronary heart disease(CHD) by population expression level and transcriptome sequencing.Methods:A total of 151 CHD patients admitted to the First Affiliated Hospital of Guangxi Medical University were selected as the CHD group, and healthy physical examination subjects were selected as the healthy control group.Real-time fluorescence quantitative polymerase chain reaction(RT-qPCR)was used to detect the expression level of hsa-miR-423-5p in peripheral blood leukocytes.Spearman correlation analysis was performed to analyze the correlation between hsa-miR-423-5p and various clinical indicators.Subcellular localization experiments and transcriptome sequencing were conducted after overexpression of hsa-miR-423-5p in EA.hy 926 cells.The sequencing results were used to predict the potential target genes of hsa-miR-423-5p, and RT-qPCR experiments were performed to validate and analyze the correlation between the target genes and hsa-miR-423-5p expression levels and various clinical indicators.Results:The expression level of hsa-miR-423-5p in peripheral blood leukocytes of the CHD group was significantly lower than that of the healthy control group(P< 0.05).Hsa-miR-423-5p expression level was negatively correlated with total cholesterol(TC)and positively correlated with high density lipoprotein cholesterol(HDLC) (P< 0.05).Subcellular localization experiments after overexpression of hsa-miR-423-5p in EA.hy 926 cells showed that hsa-miR-423-5p was mainly present in the nucleus.After transcriptome sequencing results were analyzed and validated, it was found that IL1R1 expression could be up-regulated after overexpression of hsa-miR-423-5p.The expression level of IL1R1 was lower in the CHD group than that in the healthy control group (P< 0.01), and IL1R1 expression level was positively correlated with the expression levels of hsa-miR-423-5p and HDL-C (P< 0.01).Conclusion:The expressions of hsa-miR-423-5p and IL1R1 are low in patients with CHD and correlated with TC and HDL-C.hsa-miR-423-5p up-regulates the expression of IL1R1 in endothelial cells, thereby affecting lipid levels, suggesting that hsa-miR-423-5p may affect lipid metabolism and endothelial cell function through the regulation of IL1R1 gene, thus participating in the development of CHD.
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