MiR-9 reduces human acyl-coenzyme A:cholesterol acyltransferase-1 to decrease THP-1 macrophage-derived foam cell formation

Jiajia Xu, Guangjing Hu, Ming Lu, Ying Xiong, Qin Li, Catherine C.Y. Chang, Baoliang Song, Tayuan Chang and Boliang Li

Acta Biochim Biophys Sin (Shanghai). 2013 Nov;45(11):953-62. doi: 10.1093/abbs/gmt096

1State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China

MicroRNAs (miRNAs) post-transcriptionally regulate gene expression by targeting mRNAs and control a wide range of biological functions. Recent studies have indicated that miRNAs can regulate lipid and cholesterol metabolism in mammals. Acyl-coenzyme A:cholesterol acyltransferase (ACAT) is a key enzyme in cellular cholesterol metabolism. The accumulated cholesteryl esters are mainly synthesized by ACAT1 during the formation of foam cell, a hallmark of early atherosclerotic lesions. Here, we revealed that miR-9 could target the 3′-untranslated region of human ACAT1 mRNA, specifically reduce human ACAT1 or reporter firefly luciferase (Fluc) proteins but not their mRNAs in different human cell lines, and functionally decrease the formation of foam cells from THP-1-derived macrophages. Our findings suggest that miR-9 might be an important regulator in cellular cholesterol homeostasis and decrease the formation of foam cells in vivo by reducing ACAT1 proteins.

图例: 外源miR-9抑制ACAT1的表达

全文: http://abbs.oxfordjournals.org/content/45/11/953.full