Institute of Molecular Biology & Genetics, Seoul National University, Kwanak-Gu, Seoul, Republic of Korea.
Biochem Biophys Res Commun. 2010 Feb 12;392(3):323-8. doi: 10.1016/j.bbrc.2010.01.012. Epub 2010 Jan 7.
microRNAs (miRNAs) are non-coding small RNAs regulating gene expression, cell growth, and differentiation. Although several miRNAs have been implicated in cell growth and differentiation, it is barely understood their roles in adipocyte differentiation. In the present study, we reveal that miR-27a is involved in adipocyte differentiation by binding to the PPARgamma 3'-UTR whose sequence motifs are highly conserved in mammals. During adipogenesis, the expression level of miR-27a was inversely correlated with that of adipogenic marker genes such as PPARgamma and adiponectin. In white adipose tissue, miR-27a was more abundantly expressed in stromal vascular cell fraction than in mature adipocyte fraction. Ectopic expression of miR-27a in 3T3-L1 pre-adipocytes repressed adipocyte differentiation by reducing PPARgamma expression. Interestingly, the level of miR-27a in mature adipocyte fraction of obese mice was down-regulated than that of lean mice. Together, these results suggest that miR-27a would suppress adipocyte differentiation through targeting PPARgamma and thereby down-regulation of miR-27a might be associated with adipose tissue dysregulation in obesity.
microRNAs (miRNAs) 是一种非编码的小分子 RNA，能够调控基因表达、细胞生长和分化。尽管已经有一些 miRNA 被认为与细胞生长和分化有关，但它们在脂肪细胞分化中的作用还知之甚少。在本研究中，我们发现 miR-27a 通过与 PPARγ 3'-UTR 结合，参与脂肪细胞分化，其序列基序在哺乳动物中高度保守。在脂肪生成过程中，miR-27a 的表达水平与脂肪生成标志物基因（如 PPARγ 和脂联素）呈负相关。在白色脂肪组织中，miR-27a 在基质血管细胞部分的表达量高于成熟脂肪细胞部分。在 3T3-L1 前脂肪细胞中异位表达 miR-27a 通过降低 PPARγ 的表达来抑制脂肪细胞分化。有趣的是，肥胖小鼠成熟脂肪细胞部分的 miR-27a 水平低于瘦小鼠。总之，这些结果表明，miR-27a 通过靶向 PPARγ 抑制脂肪细胞分化，因此 miR-27a 的下调可能与肥胖相关的脂肪组织失调有关。
