College of Animal Science, Shanxi Agricultural University, Taigu, China.
Anim Sci J. 2021 Jan-Dec;92(1):e13661. doi: 10.1111/asj.13661.
MicroRNAs (miRNAs) regulate adipogenic differentiation in stromal vascular fractions (SVFs) through post-transcriptional regulation of transcription factors and other functional genes. miR-301 and the homeobox C8 (HOXC8) gene are involved in lipid homeostasis; however, their roles in the adipogenic differentiation of ovine SVFs are unknown. Here, we explored the effects of miR-301 and HOXC8 on adipogenic differentiation in ovine SVFs and the regulatory role of miR-301a in HOXC8 expression. Additionally, we evaluated the effect of miR-301a and HOXC8 on the mRNA abundance of adipogenic markers and the ability of ovine SVFs to accumulate lipids. We found that miR-301a regulates adipogenic differentiation in ovine SVFs by directly targeting the 3'-untranslated region of HOXC8, resulting in significant downregulation of the HOXC8 mRNA and protein. Moreover, miR-301a overexpression suppressed adipogenic differentiation in ovine SVFs and significantly inhibited the expression of adipogenesis-related genes-including adiponectin, C/EBPα, PPARγ, and FABP4. Conversely, HOXC8 overexpression in ovine SVFs increased the accumulation of lipid droplets and remarkably promoted the expression of adipogenic markers. Taken together, our results indicate that miR-301a attenuates the adipogenic differentiation of ovine SVFs by targeting HOXC8. These findings improve our understanding of the mechanism of lipid accumulation and metabolism in sheep.
微小 RNA（miRNAs）通过转录因子和其他功能基因的转录后调控，调节基质血管部分（SVFs）的脂肪生成分化。miR-301 和同源盒 C8（HOXC8）基因参与脂质稳态；然而，它们在绵羊 SVFs 的脂肪生成分化中的作用尚不清楚。在这里，我们研究了 miR-301 和 HOXC8 对绵羊 SVFs 脂肪生成分化的影响，以及 miR-301a 对 HOXC8 表达的调节作用。此外，我们评估了 miR-301a 和 HOXC8 对脂肪生成标志物 mRNA 丰度的影响，以及绵羊 SVFs 积累脂质的能力。我们发现，miR-301a 通过直接靶向 HOXC8 的 3'非翻译区来调节绵羊 SVFs 的脂肪生成分化，导致 HOXC8 mRNA 和蛋白的显著下调。此外，miR-301a 的过表达抑制了绵羊 SVFs 的脂肪生成分化，并显著抑制了脂肪生成相关基因的表达，包括脂联素、C/EBPα、PPARγ 和 FABP4。相反，HOXC8 在绵羊 SVFs 中的过表达增加了脂滴的积累，并显著促进了脂肪生成标志物的表达。综上所述，我们的研究结果表明，miR-301a 通过靶向 HOXC8 来抑制绵羊 SVFs 的脂肪生成分化。这些发现提高了我们对绵羊脂质积累和代谢机制的理解。
