MiR-144-3p Targets FoxO1 to Reduce Its Regulation of Adiponectin and Promote Adipogenesis.
MiR-144-3p Targets FoxO1 to Reduce Its Regulation of Adiponectin and Promote Adipogenesis.
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MiR-144-3p 靶向 FoxO1，减少其对脂联素的调节并促进脂肪生成
DOI：
10.3389/fgene.2020.603144
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发表时间：
2020
影响因子：
3.7
通讯作者：
Chen J
中科院分区：
文献类型：
--
作者：
Lin W;Tang Y;Zhao Y;Zhao J;Zhang L;Wei W;Chen J
microRNAs（miRNAs）是一类重要的短链非编码RNA，在包括脂肪形成在内的多种生物学活动中发挥着重要的转录后作用。miR-144在II型糖尿病（T2 D）中显著上调，并且被认为是T2 D的重要生物标志物。然而，尽管T2 D的发生与脂肪生成有着千丝万缕的联系，但miR-144是否直接调控脂肪生成仍有待进一步探讨。在本文中，我们证明了miR-144在猪高背膘组中具有更高的表达水平，并且它对促进前脂肪细胞的分化具有显著的积极作用。FoxO 1是miR-144的靶基因，抑制前脂肪细胞的分化。另一方面，我们证明FoxO 1可以与AdipoQ基因启动子结合，然后通过与AdipoQ启动子-1，499到-1，489 bp和-1，238到-1，228 bp区域的FoxO 1结合位点结合来调节AdipoQ的表达，特别是-1，499到-1，489 bp区域。同时，miR-144和FoxO 1共表达研究也表明，这两种因子均调控脂肪形成。综上所述，我们的研究表明miR-144靶向FoxO 1，从而降低其表达，抑制其对脂联素的促进作用，从而减轻脂联素对脂肪生成的抑制作用。
MicroRNAs (miRNAs), as a series of important short-chain non-coding RNAs, play an important post-transcriptional role in many biological activities, including adipogenesis. miR-144 is significantly upregulated in type II diabetes (T2D), and is considered to be an important biomarker for T2D. However, although the occurrence of T2D is inextricably linked to adipogenesis, whether miR-144 directly regulates adipogenesis remains to be further explored. In this paper, we demonstrate that miR-144 has a higher expression level in a porcine high backfat group, and it has a significant positive effect on promoting the differentiation of pre-adipocytes. FoxO1 is a target gene of miR-144, and inhibits the differentiation of pre-adipocytes. On the other hand, we demonstrate that FoxO1 can bind to the AdipoQ gene promoter, then regulate the AdipoQ expression by binding to the FoxO1 binding site in the AdipoQ promoter -1,499 to -1,489 bp and -1,238 to -1,228 bp regions, especially the -1,499 to -1,489 bp region. Meanwhile, miR-144 and FoxO1 co-expressional research has also shown that both factors regulate adipogenesis. To sum up, our research indicates that miR-144 targets FoxO1, thus reducing its expression and inhibiting its promotional effect on adiponectin, thereby alleviating the inhibitory effect of adiponectin on adipogenesis.
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