MicroRNA let-7 Regulates 3T3-L1 Adipogenesis
MicroRNA let-7 Regulates 3T3-L1 Adipogenesis
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DOI：
10.1210/me.2008-0298
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发表时间：
2009-06-01
影响因子：
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通讯作者：
Mangelsdorf, David J.
中科院分区：
文献类型：
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作者：
Sun, Tingwan;Fu, Mingui;Mangelsdorf, David J.
3 T3-L1细胞分化为脂肪细胞涉及一系列高度协调的事件，包括克隆扩增、生长停滞和终末分化。协调这些不同步骤的机制尚不完全清楚。在这里，我们研究了microRNAs（miRNAs）是否在这一过程中发挥作用。微阵列分析检测3 T3-L1前脂肪细胞分化过程中miRNA的表达。几种miRNAs，包括let-7，在3 T3-L1脂肪形成过程中上调。let-7异位导入3 T3-L1细胞抑制克隆扩增以及终末分化。在3 T3-L1细胞脂肪形成过程中，编码高迁移率族AT-钩2（HMGA 2）（一种在其他情况下调节生长和增殖的转录因子）的mRNA与let-7水平呈负相关，let-7显著降低HMGA 2浓度。HMGA 2的敲低抑制3 T3-L1分化。这些结果表明，let-7在脂肪细胞分化中起着重要作用，并且它部分地通过靶向HMGA 2来实现，从而调节从克隆扩增到终末分化的转变。（分子内分泌学23：925-931，2009）
Differentiation of 3T3-L1 cells into adipocytes involves a highly orchestrated series of events including clonal expansion, growth arrest, and terminal differentiation. The mechanisms coordinating these different steps are not yet fully understood. Here we investigated whether microRNAs (miRNAs) play a role in this process. Microarray analysis was performed to detect miRNA expression during 3T3-L1 preadipocyte differentiation. Several miRNAs, including let-7, were up-regulated during 3T3-L1 adipogenesis. Ectopic introduction of let-7 into 3T3-L1 cells inhibited clonal expansion as well as terminal differentiation. The mRNA encoding high-mobility group AT-hook 2 (HMGA2), a transcription factor that regulates growth and proliferation in other contexts, was inversely correlated with let-7 levels during 3T3-L1 cell adipogenesis, and let-7 markedly reduced HMGA2 concentrations. Knockdown of HMGA2 inhibited 3T3-L1 differentiation. These results suggest that let-7 plays an important role in adipocyte differentiation and that it does so in part by targeting HMGA2, thereby regulating the transition from clonal expansion to terminal differentiation. (Molecular Endocrinology 23: 925-931, 2009)