miR-let-7c参与胆固醇代谢，但其在巨噬细胞脂质蓄积中的作用尚未阐明。PGC-1α可促进ABCA1表达抑制巨噬细胞脂质蓄积。生物信息学及预实验发现miR-let-7c可能靶向沉默PGC-1α。本项目拟用报告基因明确miR-let-7c对PGC-1α的直接作用，观察miR-let-7c对巨噬细胞脂质蓄积和ABCA1表达的影响，探讨PGC-1α在miR-let-7c调控ABCA1表达中的作用，整体上评价miR-let-7c对PGC-1α和As的作用。预实验发现miR-let-7c可能受lncRNA Kcnq1ot1的调控，我们将用miR-let-7c sensor和RNA pull-down等实验探讨miR-let-7c的受调控机制，以及miR-let-7c在lncRNA Kcnq1ot1调控细胞脂质蓄积中的作用。项目的完成有望为体内调控巨噬细胞脂质蓄积和As防治提供新的靶点和理论依据。

MiR-let-7c is involved in cholesterol metabolism, but its role in the accumulation of lipid in macrophages has not been elucidated. PGC-1α can promote ABCA1 expression to inhibit the accumulation of lipid in macrophages. Bioinformatics and preliminary experiments have found that miR-let-7c may inhibit peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) expression. The project will investigate more deeply on the direct effects of miR-let-7c on PGC-1α by report gene systems. In vitro experiments observe the effects of miR-let-7c on lipid accumulation and the expression of ABCA1.Then we explore the role of PGC-1α in regulation of ABCA1 expression by miR-let-7c. Furthermore, we evaluate the regulatory role of miR-let-7c on PGC-1α expression and plaque progression at systematic level. We found that miR-let-7c might be regulated by lncRNA Kcnq1ot1 through preliminary experiments. We will explore the upstream regulatory mechanisms of miR-let-7c by miR-let-7c sensor and RNA pull-down methods. In addition, the roles of miR-let-7c in lncRNA Kcnq1ot1 regulating accumulation of lipid in macrophages will be investigated. The completion of the project is expected to provide new targets and theoretical basis for the regulation of lipid accumulation of macrophages and the prevention and treatment of As in vivo.