Department of Geriatrics, Zhejiang Provincial People's Hospital, Hangzhou, PR China.
FEBS Lett. 2012 May 21;586(10):1472-9. doi: 10.1016/j.febslet.2012.03.068. Epub 2012 Apr 18.
Cellular cholesterol levels are tightly regulated and represent a balance of cholesterol uptake, endogenous synthesis and efflux. Although the classic transcriptional regulations of cholesterol metabolism by liver X receptors (LXRs) have been well studied, the potential effects of LXR-responsive microRNAs (miRNAs) still need to be unveiled. Here, we describe that miR-26, an LXR-suppressed miRNA, inhibits the expression of the ATP-binding cassette transporter A1 (ABCA1) and ADP-ribosylation factor-like 7 (ARL7), two LXR target genes which play critical roles in cholesterol efflux. These findings have not only figured out an alternative mechanism for LXR regulation, but also provided a potential therapeutic target for cholesterol metabolic disorders.
细胞内胆固醇水平受到严格调控,反映了胆固醇摄取、内源性合成和外排之间的平衡。尽管肝 X 受体 (LXRs) 对胆固醇代谢的经典转录调控已得到深入研究,但 LXR 反应性 microRNAs (miRNAs) 的潜在作用仍有待揭示。在这里,我们描述了 miR-26,一种受 LXR 抑制的 miRNA,可抑制 ATP 结合盒转运蛋白 A1 (ABCA1) 和 ADP-核糖基化因子样 7 (ARL7) 的表达,这两个基因是胆固醇外排的关键 LXR 靶基因。这些发现不仅为 LXR 调节提供了一种替代机制,也为胆固醇代谢紊乱提供了一个潜在的治疗靶点。