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微小RNA-144通过介导C/EBPα-FOXO1蛋白复合物的形成来调节脂肪生成。

MiR-144 regulates adipogenesis by mediating formation of C/EBPα-FOXO1 protein complex.

作者信息

Lin Weimin, Wen Xianyu, Li Xuexin, Chen Lei, Wei Wei, Zhang Lifan, Chen Jie

机构信息

College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.

College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.

出版信息

Biochem Biophys Res Commun. 2022 Jul 5;612:126-133. doi: 10.1016/j.bbrc.2022.04.093. Epub 2022 Apr 28.

Abstract

CeRNA effect was an important regulation mode of miRNA mediated bio-activities, however, most of the researches of ceRNA were on ncRNAs synergetic with mRNAs, the exploration of ceRNA effect regulated mRNA interaction was still lack of. Besides, C/EBPα was one of the most crucial adipogenic regulators, which has been demonstrated to form a protein complex with FOXO1 to mediate AdipoQ expression. So that, we try to explore whether the ceRNA effect mediated the interaction of C/EBPα and FOXO1, and identified the key miRNAs of their ceRNA effect. In this paper, we found the ceRNA effect of C/EBPα and FOXO1 mediated their protein complex formation, furthermore regulated its transcriptional role for AdipoQ, thereby influencing pre-adipocytes adipogenesis. More importantly, we demonstrated that the miR-144 was the decisive factor that mediated the ceRNA effect of C/EBPα and FOXO1 to influence AdipoQ, thus regulated pre-adipocytes adipogenesis. This research will provide a new supplementary idea of the miRNA role in mediating coding RNA interaction that regulates pre-adipocyte adipogenesis.

摘要

竞争性内源RNA(ceRNA)效应是微小RNA(miRNA)介导生物活性的一种重要调控模式,然而,大多数ceRNA研究集中在与信使核糖核酸(mRNA)协同作用的非编码核糖核酸(ncRNA)上,对ceRNA效应调控mRNA相互作用的探索仍很缺乏。此外,CCAAT增强子结合蛋白α(C/EBPα)是最重要的脂肪生成调节因子之一,已证明它能与叉头框蛋白O1(FOXO1)形成蛋白复合物以介导脂联素(AdipoQ)的表达。因此,我们试图探究ceRNA效应是否介导了C/EBPα与FOXO1的相互作用,并鉴定出其ceRNA效应的关键miRNA。在本文中,我们发现C/EBPα与FOXO1的ceRNA效应介导了它们的蛋白复合物形成,进而调节其对AdipoQ的转录作用,从而影响前脂肪细胞的脂肪生成。更重要的是,我们证明了miR-144是介导C/EBPα与FOXO1的ceRNA效应以影响AdipoQ从而调节前脂肪细胞脂肪生成的决定性因素。本研究将为miRNA在介导编码RNA相互作用以调节前脂肪细胞脂肪生成方面的作用提供新的补充思路。

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