miR-17 targets IGF-1 to regulate vascular smooth muscle cell proliferation in coronary artery disease / 西安交通大学学报(医学版)

ABSTRACT

【Objective】 To investigate the potential mechanism of miR-17 in vascular smooth muscle cells in coronary artery disease (CAD). 【Methods】 mRNA expression of miR-17 and insulin growth factor 1 (IGF-1) in serum and VSMCs of CAD patients were detected by RT-qPCR. Potential targets of miR-17 were detected by bioinformatics and luciferase reporter assay; CCK-8 and cloning formation assay was performed to measure the proliferation of VSMCs. 【Results】 RT-qPCR results showed that compared with those in control group, the miR-17 mRNA expression in VSMCs and serum of CAD patients were significantly upregulated (P<0.01). The results of CCK-8 and clone formation assay showed that compared with those in control group, the number of VSMCs proliferation and cloning formation in the miR-17 overexpression group were significantly increased (P<0.01); those in the miR-17 low expression group were significantly reduced (P<0.01). Bioinformatics analysis showed that the 3’-UTR of IGF-1 had an miR-17 binding site. The luciferase reporter assay showed that the luciferase activity of VSMCs co-transfected with wild-type IGF-1 plasmid and miR-17 mimic was increased (P<0.001). However, the luciferase activity of VSMCs transfected with mutant IGF-1 plasmid and miR-17 mimics remained unchanged. Compared with that in control group, the expression of IGF-1 in VSMCs was upregulated after miR-17 overexpression (P<0.01). And the number of VSMCs proliferation and clone formation in the IGF-1 overexpression group was significantly increased (P<0.05). 【Conclusion】 miR-17 promotes the proliferation of VSMCs by targeting IGF-1. This indicates that miR-17 can be used as a predictive biomarker of CAD, and IGF-1 may be a potential therapeutic target.