LncRNA FOXC2-AS1 regulated proliferation and apoptosis of vascular smooth muscle cell through targeting miR-1253/FOXF1 axis in atherosclerosis

Y.-Q. Wang, Z.-M. Xu, X.-L. Wang, J.-K. Zheng, Q. Du, J.-X. Yang, H.-C. Zhang

Department of Cardiology, Affiliated Hospital of North Sichuan Medical College, Nanchong, Sichuan Province, China. 39770191@qq.com

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• Cardiology

OBJECTIVE: Atherosclerosis (AS) is the most dangerous factor for human death, which is responsible for coronary heart disease. Growing evidence has showed that long non-coding RNAs (lncRNAs) are involved in the development of AS. In this study, we mainly aimed at investigating the roles of FOXC2-AS1 in AS patients.

PATIENTS AND METHODS: RT-PCR was performed to detect the expressions of FOXC2-AS1 and miR-1253 in serum samples of AS patients (n=35) and healthy volunteer (n=35). The correlation between FOXC2-AS1 and miR-1253 was further analyzed. Human vascular smooth muscle cells (VSMCs) were respectively treated with ox-LDL, IL-6, CRP, TNF-α and IL-8 to explore the affecting factors. P-FOXC2-AS1 was constructed and transfected into VSMCs. Cell proliferation abilities were measured by CCK-8 assay. Cell apoptotic rates were measured by flow cytometry (FACS) analysis. Western blot (WB) was performed to detect protein levels of FOXF1, Bcl-2, Bax and Cleaved Caspase3. Finally, luciferase gene reporter assay was performed to prove the relationships between FOXC2-AS1 and miR-1253, miR-1253 and FOXF1.

RESULTS: We found that FOXC2-AS1 was significantly upregulated in AS patients, which could be induced by ox-LDL and IL-6 in VSMCs. MiR-1253 was decreased in AS patients, which was negatively correlated with FOXC2-AS1. Furthermore, FOXC2-AS1 overexpression promoted proliferation and inhibited apoptosis in VSMCs. Luciferase gene reporter assay showed that FOXC2-AS1 could bind to miR-1253 in VSMCs and 293 cells. Moreover, miR-1253 overexpression inhibited proliferation and promoted apoptosis of VSMCs. Luciferase reporter assay proved that miR-1253 could target at FOXF1 in VSMCs and 293 cells, which was reported to be associated with cell proliferation and apoptosis in some cancers. Additionally, miR-1253 mimic or GSK343, a FOXF1 inhibitor, was respectively transfected into VSMCs with p-FOXC2-AS1. Results showed that the promoted cell proliferation and inhibited cell apoptosis were reversed as well, confirming that FOXC2-AS1 promoted cell proliferation and inhibited apoptosis via miR-1253/FOXF1 signaling axis in AS patients.

CONCLUSIONS: According to the results, we found that FOXC2-AS1 was upregulated in AS patients; furthermore, FOXC2-AS1 overexpression promoted cell proliferation and inhibited cell apoptosis via targeting miR-1253/FOXF1 signaling axis. Our results elucidated a potential mechanism underlying the role of FOXC2-AS1, which might be used as a promising marker and a potential target for AS patients.

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