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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130
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miR-17-92 cluster accelerates adipocyte differentiation by negatively regulating tumor-suppressor Rb2/p130

机译：miR-17-92簇通过负调控肿瘤抑制因子Rb2 / p130加速脂肪细胞分化

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摘要

Adipogenesis involves cell proliferation and differentiation, both of which have been shown to be regulated by micro (mi)RNA. During mouse preadipocyte 3T3L1 cell differentiation, we found that miR-17-92, a miRNA cluster that promotes cell proliferation in various cancers, was significantly up-regulated at the clonal expansion stage of adipocyte differentiation. Stable transfection of 3T3L1 cells with miR-17-92 resulted in accelerated differentiation and increased tri-glyceride accumulation after hormonal stimulation. By using a lucif-erase reporter assay, we demonstrated that miR-17-92 directly targeted the 3' UTR region of Rb2/p130, accounting for subsequently reduced Rb2/p130 mRNA and protein quantities at the stage of clonal expansion. siRNA-mediated knock-down of Rb2/p130 at the same stage of clonal expansion recapitulated the phenotype of overex-pression of miR-17-92 in the stably transfected 3T3L1 cells. These data indicate that miR-17-92 promotes adipocyte differentiation by targeting and negatively regulating Rb2/p130.
机译：脂肪生成涉及细胞增殖和分化，这两者均已显示受微（mi）RNA调节。在小鼠前脂肪细胞3T3L1细胞分化过程中，我们发现miR-17-92（一种在各种癌症中促进细胞增殖的miRNA簇）在脂肪细胞分化的克隆扩增阶段显着上调。用miR-17-92稳定转染3T3L1细胞会导致激素刺激后加速分化并增加甘油三酸酯的积累。通过使用萤光素酶报告基因测定，我们证明了miR-17-92直接靶向Rb2 / p130的3'UTR区，从而解释了随后在克隆扩增阶段减少的Rb2 / p130 mRNA和蛋白质数量。在稳定扩增的3T3L1细胞中，siRNA介导的Rb2 / p130的敲低在克隆扩增的同一阶段概括了miR-17-92过表达的表型。这些数据表明，miR-17-92通过靶向和负调控Rb2 / p130促进脂肪细胞分化。

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