Long non-coding RNA ADNCR suppresses adipogenic differentiation by targeting miR-204
Long non-coding RNA ADNCR suppresses adipogenic differentiation by targeting miR-204
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长非编码RNA ADNCR通过靶向miR-204抑制脂肪形成分化
DOI：
10.1016/j.bbagrm.2016.05.003
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发表时间：
2016-07-01
影响因子：
4.7
通讯作者：
Chen, Hong
中科院分区：
文献类型：
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作者：
Li, Mingxun;Sun, Xiaomei;Chen, Hong
成脂是一个由成脂调节因子网络调控的复杂而精确的过程。一些研究已经强调了lncRNAs在脂肪细胞分化中的相关性，但确切的分子机制在很大程度上仍然难以捉摸。在本研究中，我们用Ribo-Zero RNA-Seq技术研究了体外培养的牛前脂肪细胞和分化的脂肪细胞的聚(A)+和聚(A)-lncRNA。最终确定了一组严格的2882个LncRNA。对lncRNAs表达谱的比较表明，16个lncRNAs在脂肪细胞分化过程中存在差异表达。我们专注于下调最多的lncRNA，我们将其命名为脂肪细胞分化相关的长非编码RNA(ADNCR)。在机制上，ADNCR通过与miR-204竞争的内源性RNA(CerNA)来抑制脂肪细胞的分化，从而增强miR-204靶基因SIRT1的表达，SIRT1通过与NCoR和SMART对接抑制PPARγ活性来抑制脂肪细胞的分化和成脂基因的表达。我们的数据不仅为鉴定在脂肪细胞分化中具有功能作用的lncRNAs提供了宝贵的基因组资源，而且为理解成脂分化的机制提供了新的见解。(C)2016爱思唯尔B.V.保留所有权利。
Adipogenesis is a complex and precisely orchestrated process mediated by a network of adipogenic regulatory factors. Several studies have highlighted the relevance of lncRNAs in adipocyte differentiation, but the precise molecular mechanism has largely remained elusive. In the present study, we performed Ribo-Zero RNA-Seq to investigate both the poly(A) + and poly(A)-lncRNAs of in vitro cultured bovine preadipocytes and differentiated adipocytes. A stringent set of 2882 lncRNAs was finally identified. A comparison of the lncRNAs expression profiles revealed that 16 lncRNAs are differentially expressed during adipocyte differentiation. We focused on the most downregulated lncRNA, which we named adipocyte differentiation-associated long noncoding RNA (ADNCR). Mechanistically, ADNCR inhibited adipocyte differentiation by functioning as a competing endogenous RNA (ceRNA) for miR-204, thereby augmenting the expression of the miR-204 target gene, SIRT1, which is known to inhibit adipocyte differentiation and adipogenic gene expression by docking with NCoR and SMART to repress PPAR gamma activity. Our data not only provide a valuable genomic resource for the identification of lncRNAs with functional roles in adipocyte differentiation but also reveal new insights into understanding the mechanisms of adipogenic differentiation. (C) 2016 Elsevier B.V. All rights reserved.