Lin Weimin, Wen Xianyu, Li Xuexin, Chen Lei, Wei Wei, Zhang Lifan, Chen Jie
College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.
College of Animal Science & Technology, Nanjing Agricultural University, Nanjing, Jiangsu, 210095, China.
Biochem Biophys Res Commun. 2022 Jul 5;612:126-133. doi: 10.1016/j.bbrc.2022.04.093. Epub 2022 Apr 28.
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.
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。
