Abstract

Background It 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). Methods Human 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. Results The 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. Conclusion MiR-135a-5p suppresses VSMCs proliferation and migration induced by ox-LDL via targeting and activating FOXO1/Cyclin D1 and JAK2/STAT3 signaling pathways .