miR-296-5p标靶USP22调控巨噬细胞极化在动脉粥样硬化中的作用及机制研究

miR-296-5p在动脉粥样硬化（As）斑块内高表达，但其作用机制不清。前期，我们进行了生物信息学分析，发现miR-296-5p与泛素特异性肽酶22（USP22）存在靶向结合，而USP22下游因子RNA聚合酶II转录亚基1调停物（MED1）已被报道可调节巨噬细胞极化并影响As进程。预实验结果亦证实miR-296-5p能抑制USP22和MED1表达，故我们推测miR-296-5p可通过USP22/MED1途径调控巨噬细胞极化和As发展。为此，本研究拟采用体外实验明确miR-296-5p对巨噬细胞极化的影响；双荧光素酶报告基因验证miR-296-5p与USP22的靶向关系；并深入探讨USP22和MED1在miR-296-5p调控巨噬细胞极化中的作用；最后通过动物实验观察miR-296-5p在体内对巨噬细胞极性、USP22/MED1表达和As斑块的影响，以期为As的防治提供新策略。

miR-296-5p is highly expressed in atherosclerotic plaque, but its mechanism of action remains unclear. In our previous work, we performed bioinformatic analysis and found that miR-296-5p contained a potential binding site for ubiquitin-specific peptidase 22 (USP22) , whose downstream factor "mediator of RNA polymerase II transcription subunit 1 (MED1)" has been implicated in macrophage polarization and atherosclerosis progression. Also, our preliminary data demonstrated that miR-296-5p could inhibit the expression of USP22 and MED1. Thus, we speculate that miR-296-5p regulates macrophage polarization and atherosclerosis through the USP22/MED1 pathway. In this study, we determine the effect of miR-296-5p on macrophage polarization using in vitro experiments. We also perform dual-luciferase reporter gene assays to verify the targeted relationship between miR-296-5p and USP22. Furthermore, we investigate the roles of USP22 and MED1 in miR-296-5p regulation of macrophage polarization. Finally, we observe the in vivo effect of miR-296-5p on macrophage polarization, USP22/MED1 expression and atherosclerotic plaque using animal experiments. This study aims to provide a new strategy for the prevention and treatment of atherosclerosis.