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环状异柠檬酸脱氢酶2通过miR-193a-5p/4轴调控猪脂肪生成:对ceRNA介导的脂肪沉积调控的启示

CircIDH2 Modulates Porcine Adipogenesis via the miR-193a-5p/4 Axis: Implications for ceRNA-Mediated Regulation of Fat Deposition.

作者信息

Li Meng, Chen Jiayi, Bao Wu, Ma Shuangji, Wen Mingxin, Han Yuqi, Zhang Wanfeng, Yang Yang, Guo Xiaohong, Li Bugao

机构信息

College of Animal Science, Shanxi Agricultural University, Jinzhong 030801, China.

出版信息

Cells. 2025 Aug 15;14(16):1265. doi: 10.3390/cells14161265.

DOI:10.3390/cells14161265
PMID:40862743
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12384935/
Abstract

Adipose tissue development plays a critical role in determining carcass quality and meat production efficiency in swine; however, the regulatory mechanisms governing fat deposition remain incompletely understood. Circular RNAs (circRNAs), characterized by high stability and resistance to RNase R degradation, have emerged as important epigenetic regulators of livestock traits. This study investigated the regulatory role of circIDH2 in adipogenic differentiation of porcine preadipocytes and the underlying molecular mechanisms. Functional assays revealed that silencing circIDH2 markedly promoted preadipocyte proliferation while inhibiting differentiation and lipid accumulation; conversely, circIDH2 overexpression produced the opposite effects. Mechanistically, circIDH2 acted as a molecular sponge for miR-193a-5p through complementary base pairing, thereby relieving the repression of its target gene 4, a positive regulator of adipogenesis. Furthermore, this study demonstrated that miR-193a-5p promoted proliferation but suppressed the differentiation of porcine preadipocytes, whereas 4 inhibited proliferation while promoting adipogenic differentiation. Rescue experiments further confirmed the regulatory relationship among circIDH2, miR-193a-5p, and 4. In summary, the findings indicated that circIDH2 functioned as a key regulator of adipogenesis by modulating the miR-193a-5p/4 axis, thereby suppressing preadipocyte proliferation and promoting adipogenic differentiation. These results provide a theoretical foundation for future investigations into the regulatory mechanisms of adipose tissue development.

摘要

脂肪组织发育在决定猪的胴体品质和肉类生产效率方面起着关键作用;然而,脂肪沉积的调控机制仍未完全明确。环状RNA(circRNA)具有高稳定性和抗RNase R降解的特点,已成为家畜性状的重要表观遗传调控因子。本研究探讨了circIDH2在猪前体脂肪细胞成脂分化中的调控作用及其潜在分子机制。功能分析表明,沉默circIDH2显著促进前体脂肪细胞增殖,同时抑制分化和脂质积累;相反,circIDH2过表达则产生相反的效果。机制上,circIDH2通过互补碱基配对作为miR-193a-5p的分子海绵,从而解除对其靶基因4(成脂的正向调节因子)的抑制。此外,本研究表明miR-193a-5p促进猪前体脂肪细胞增殖但抑制其分化,而4抑制增殖同时促进成脂分化。拯救实验进一步证实了circIDH2、miR-193a-5p和4之间的调控关系。总之,研究结果表明circIDH2通过调节miR-193a-5p/4轴发挥成脂关键调节因子的作用,从而抑制前体脂肪细胞增殖并促进成脂分化。这些结果为未来研究脂肪组织发育的调控机制提供了理论基础。

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