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

Yongfeng Zhang,Ping Yan,Min Chu,Xian Guo,Chunnian Liang,Pengjia Bao,Yarong Gu,Xuezhi Ding,Lanhua Ma,Yongfang Chang

doi:10.3390/biology10100949

Abstract

Simple SummaryYak 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.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.

Highlights

The yak (Bos grunniens) is an animal of economic importance living in the adjacent areas of the Qinghai-Tibetan Plateau and is the only livestock resource that can make full use of natural pasture resources for animal production, and its wool, meat, milk and other by-products provide an effective livelihood and economic source for local nomadic herders [1,2,3]
By comparing the expression of bta-miR-2400 in different yak tissues, we found that bta-miR-2400 was highly expressed in adipose tissue (Figure 1A), and bta-miR-2400 expression was sharply decreased at 36 months compared to 18 months in adipose tissue (Figure 1B)
We examined the expression of bta-miR-2400 during the yak preadipocytes differentiation

Summary

Introduction

The yak (Bos grunniens) is an animal of economic importance living in the adjacent areas of the Qinghai-Tibetan Plateau and is the only livestock resource that can make full use of natural pasture resources for animal production, and its wool, meat, milk and other by-products provide an effective livelihood and economic source for local nomadic herders [1,2,3]. As endogenous non-coding RNAs, miRNAs are found in the genomes of plants and animals in the form of single-copy, multi-copy and gene clusters [9,10] They are involved in the growth and development of different species, tissues, organs, and participated in the regulation of gene expression through specific binding to degrade target mRNA or block the post-transcriptional translation of target mRNAs [11]. MiR-181a-5p targets and downregulates TCF7L2 expression to increase C/EBPα and PPARγ expression, promoting adipogenesis while inactivating Wntregulated gene transcription by binding to β-catenin [17]. These studies demonstrate that miRNAs play an essential role in adipogenesis and fat metabolism

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Conclusion