microRNA是一类在基因转录后过程中通过对靶mRNA的翻译抑制和降解,对基因表达起负调控作用的小的非编码RNA分子。细胞内脂类代谢除了受固醇调节元件结合蛋白(SREBP)与肝x受体α(LXRa)这两个典型的转录因子调控外,还受到多种miRNA的调控。miR.33是定位于SREBP基因内含子的miRNA,其通过抑制ABCA1和ABCG1的表达,从而调控胆固醇输出和高密度脂蛋白代谢。除此之外,miR-33还能靶向参与脂肪酸D氧化相关基因CPT1A、CROT和HADHB,从而减少脂肪酸的降解。除miR-33外,miR-122、miR-370、miR-378/378*、miR.302a、miR.106b等也被报道参与调控胆固醇稳态和脂肪酸代谢。这些参与调控脂类代谢miRNA的发现有可能为血脂异常和一些代谢紊乱疾病的治疗带来一些新启示。
MicroRNAs are a class of tiny noncoding RNAs, which have a critical role in posttranscriptional regulation, negatively regulating gene expression by translational repression and degradation of target mRNAs. In addition to classic transcriptional regulation of cholesterol metabolism by sterol regulatory element-binding protein and the liver X receptors, members of miRNAs have been identified to be regulators of lipid metabolism, miR-33, an intronic miRNA located within SREBP gene, regulates cholesterol efflux and high-density lipoprotein metabolism by repressing the expression of ABCA1 and ABCG1. It also can reduce fatty acid degradation by inhibiting the expression of CPTIA, CROT and HADttB, which involve in fatty acid α-oxidation. Other miRNAs including miR-122, miR-370, miR-378/378*, miR-302a and miR-106b, also play roles in regulating cholesterol homeostasis and fatty acid metabolism. Recent advances in the understanding of the regulation of lipid metabolism by miRNAs may lead to development of novel strategies for the treatment of dyslipidemias and other metabolic disorders.