MiR-301a inhibits adipogenic differentiation of adipose-derived stromal vascular fractions by targeting HOXC8 in sheep.

Abstract

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.