miR-96/miR-182/miR-183 was identified as the most upregulated miRNA in mice fed a chow diet supplemented with a mixture of lovastatin plus ezetimibe (to deplete hepatic cholesterol and enhance cholesterol biosynthesis) compared to mice fed a chow diet supplemented with cholesterol (to increase hepatic cholesterol content and inhibit cholesterol synthesis) (Jeon et al. 2013). The miR-96/miR-182/miR-183 locus is regulated by SREBP and regulates the expression of key proteins that control the maturation and activation of SREBP. miR-96 and miR-182 inhibit the expression of INSIG and FBXW7, proteins that control the retention of the SREBP/ SCAP complex in the ER and the degradation nuclear SREBP, respectively (Jeon et al. 2013). As a consequence, overexpression of all three miRNAs enhances cholesterol and fatty acid synthesis in HeLa cells. Further experiments in vivo will be important to define the specific contribution of these miRNAs in regulating hepatic lipid homeostasis and lipoprotein metabolism.

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