Bta-miR-2400 Targets SUMO1 to Affect Yak Preadipocytes Proliferation and Differentiation

SIMPLE SUMMARY: Yak adipose tissue may have evolved a unique energy metabolism manner that accommodates the organism’s seasonal growth rhythms. Rare reports have shown that miRNAs regulate lipid metabolism in domestic yaks. In the present study, miR-2400 is a novel bovine miRNA; gain- and loss- function of bta-miR-2400 were performed in Yak preadipocytes, and it was revealed that bta-miR-2400 regulates lipid metabolism and energy homeostasis in yak preadipocytes by directly targeting small ubiquitin like modifier 1 (SUMO1) to promote cell proliferation and inhibit differentiation. These findings will undoubtedly facilitate future studies of miRNA regulation in lipid metabolism in high-altitude animals. ABSTRACT: Yak adipose tissue may have evolved a unique energy metabolism manner to accommodate the organism’s seasonal growth rhythms. MiRNAs regulate multiple biological processes including systemic metabolism and energy homeostasis through post-transcriptional regulations. Rare reports have shown that miRNAs regulate lipid metabolism in domestic yaks. Therefore, we investigated the regulatory mechanisms of bta-miR-2400 in modulating yak preadipocytes proliferation and differentiation. We found that bta-miR-2400 was highly expressed in adipose tissue. Overexpression of bta-miR-2400 in yak preadipocytes significantly enhanced cell proliferation, increased the number of EdU fluorescence-stained cells, and promoted the expression of proliferation marker genes (CDK2, CDK4 and PCNA). Besides, overexpression of bta-miR-2400 repressed the expression of adipogenesis-related marker genes, and the content of cellular triglyceride was substantially reduced. Conversely, inhibition of bta-miR-2400 showed opposite effects compared to those of bta-miR-2400 overexpression in yak preadipocytes. Further, luciferase reporter assays revealed that SUMO1 is a target gene of bta-miR-2400, with bta-miR-2400 being able to down-regulate SUMO1 mRNA and protein expression. In conclusion, bta-miR-2400 regulates lipid metabolism and energy homeostasis in yak preadipocytes by directly targeting SUMO1 to promote cell proliferation and inhibit differentiation.