MiR-135a-5p inhibits vascular smooth muscle cells proliferation and migration by inactivating FOXO1 and JAK2 signaling pathway

Abstract

BackgroundIt is reportedly demonstrated that miR-135a-5p plays a critical role in cancer cells, macrophages, and endothelia cells. However, little is known concerning the function of miR-135a-5p in vascular smooth muscle cells (VSMCs) and atherosclerosis (AS). MethodsHuman VSMCs and male C57BL/6 mice were used for establishing AS cell models and animal models. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expressions of miR-135a-5p, forkhead box O1 (FOXO1) mRNA, and Janus kinase 2 (JAK2) mRNA. CCK-8, BrdU, and Transwell assays were used to detect cell migration and proliferation. Cell cycle and apoptosis were analyzed using flow cytometry. The interactions among miR-135a-5p, FOXO1 and JAK2 were validated employing Western blot, qRT-PCR and Luciferase reporter gene assay. ResultsThe expression of miR-135a-5p was significantly decreased in serum samples of AS patients, VSMCs treated with ox-LDL and AS mice models. The overexpression of miR-135a-5p induced VSMCs cycle arrest and apoptosis, and inhibited proliferation and migration. Further experiments confirmed that miR-135a-5p could target and repress FOXO1/CyclinD1 and JAK2/STAT3 pathway. Additionally, the associations among miR-135a-5p, FOXO1/Cyclin D1 and JAK2/STAT3 were validated using animal models. ConclusionMiR-135a-5p suppresses VSMCs proliferation and migration induced by ox-LDL via targeting and activating FOXO1/Cyclin D1 and JAK2/STAT3 signaling pathways.