State Key Laboratory of Molecular Biology, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai 200031, China.
Acta Biochim Biophys Sin (Shanghai). 2013 Nov;45(11):953-62. doi: 10.1093/abbs/gmt096. Epub 2013 Sep 12.
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.
MicroRNAs (miRNAs) 通过靶向 mRNAs 对基因表达进行转录后调控，控制着广泛的生物学功能。最近的研究表明，miRNAs 可以调节哺乳动物的脂质和胆固醇代谢。酰基辅酶 A：胆固醇酰基转移酶（ACAT）是细胞胆固醇代谢中的关键酶。在泡沫细胞的形成过程中，积累的胆固醇酯主要由 ACAT1 合成，泡沫细胞是早期动脉粥样硬化病变的标志。在这里，我们揭示了 miR-9 可以靶向人 ACAT1 mRNA 的 3'-非翻译区，特异性降低不同人细胞系中的人 ACAT1 或报告萤火虫荧光素酶（Fluc）蛋白，但不降低其 mRNA，并且在功能上减少了源自 THP-1 衍生的巨噬细胞的泡沫细胞的形成。我们的研究结果表明，miR-9 可能是细胞胆固醇稳态的重要调节剂，并通过降低 ACAT1 蛋白来减少体内泡沫细胞的形成。
