Down-regulation of hsa-miR-148b inhibits vascular smooth muscle cells proliferation and migration by directly targeting HSP90 in atherosclerosis

The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) are crucial pathological processes that are involved in atherosclerosis. Growing evidence suggests that microRNAs (miRNAs) play critical roles in VSMCs functions. Here, we analyzed the expression of four atherosclerosis-related miRNAs and found that hsa-miR-148b was significantly down-regulated in plaques from atherosclerotic patients compared to a healthy control group. The restoration of hsa-miR-148b function in cells transfected with a hsa-miR-148b mimicmarkedly inhibited VSMCs proliferation and migration compared to a hsa-miR-148b mimic control. Furthermore, we discovered that heat shock protein 90 (HSP90) was a direct target of hsa-miR-148b in VSMCs. Hsa-miR-148b suppressed HSP90 expression by directly binding its 3’-untranslated region (UTR). In addition, the expression of hsa-miR-148b was negatively correlated with the HSP90 mRNA levels in plaques of atherosclerotic patients. Interestingly, the overexpression of HSP90 partly abrogated the hsa-miR-148b-mediated inhibition of VSMCs proliferation and migration. Our study provides the first evidence that hsa-miR-148b has anti-proliferative and migratory functions by targeting HSP90 in VSMCs and may aidin the development of new biomarkers and potential therapeutic targets for atherosclerosis