环状BTBD7通过miR-183/SMAD4轴抑制脂肪生成。

CircBTBD7 inhibits adipogenesis via the miR-183/SMAD4 axis.

作者信息

Ma Zheng, Chen Yun, Qiu Ju, Guo Rui, Cai Keli, Zheng Yan, Zhang Yuyao, Li Xueqing, Zan Linsen, Li Anning

机构信息

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China.

College of Animal Science and Technology, Northwest A&F University, Yangling, Shaanxi 712100, PR China; National Beef Cattle Improvement Center, Northwest A&F University, Yangling, Shaanxi 712100, PR China.

出版信息

Int J Biol Macromol. 2023 Dec 31;253(Pt 2):126740. doi: 10.1016/j.ijbiomac.2023.126740. Epub 2023 Sep 9.

DOI:10.1016/j.ijbiomac.2023.126740

PMID:37689299

Abstract

Adipogenesis is a complex biological process. However, the regulatory mechanism of circRNAs in adipogenesis is still unclear. In this study, we identified a novel circRNA, circBTBD7, which was highly expressed in adipose tissue and peaked at two days after differentiation in bovine primary adipocytes. When circBTBD7 was knocked down in bovine primary adipocytes, the lipid droplets accumulation was significantly increased. Furthermore, the expression of adipocyte differentiation markers (PPARγ and C/EBPα) and lipogenic genes (FABP4, FASN and ACCα) were significantly upregulated. Moreover, circBTBD7 was mainly located in the cytoplasm, which indicated it was probably to act as competitive endogenous RNAs (ceRNAs). Subsequently, the dual luciferase reporter assay showed that circBTBD7 could bind to miR-183. Further, miR-183 promoted adipogenesis by inhibiting SMAD4. What's more, the rescue assays showed that circBTBD7 attenuated the inhibition of SMAD4 expression by sponging miR-183. In summary, these results suggested that circBTBD7 inhibited adipogenesis via the miR-183/SMAD4 axis.

摘要

脂肪生成是一个复杂的生物学过程。然而，circRNA在脂肪生成中的调控机制仍不清楚。在本研究中，我们鉴定出一种新型circRNA，即circBTBD7，其在脂肪组织中高表达，并在牛原代脂肪细胞分化后两天达到峰值。当circBTBD7在牛原代脂肪细胞中被敲低时，脂滴积累显著增加。此外，脂肪细胞分化标志物（PPARγ和C/EBPα）和生脂基因（FABP4、FASN和ACCα）的表达显著上调。此外，circBTBD7主要位于细胞质中，这表明它可能作为竞争性内源RNA（ceRNA）发挥作用。随后，双荧光素酶报告基因检测表明circBTBD7可以与miR-183结合。此外，miR-183通过抑制SMAD4促进脂肪生成。而且，拯救实验表明circBTBD7通过海绵化miR-183减弱了对SMAD4表达的抑制。总之，这些结果表明circBTBD7通过miR-183/SMAD4轴抑制脂肪生成。