Abstract
Emerging evidence suggests that long noncoding RNAs (lncRNAs) play essential roles in the regulation of gene expression. However, the functional contributions of lncRNAs to adipogenesis remain largely unexplored. In this study, we investigated global changes in the expression patterns of lncRNAs in visceral adipose tissue and identified RP11-142A22.4 as a significantly upregulated lncRNA. In isolated preadipocytes, knockdown of RP11-142A22.4 inhibited differentiation and reduced C/EBP-α and PPAR-γ expression. Investigations of the underlying mechanisms revealed that RP11-142A22.4 contains a functional miR-587 binding site. Mutation of the binding sites for RP11-142A22.4 in miR-587 abolished the interaction, as indicated by a luciferase reporter assay. Furthermore, RP11-142A22.4 affected the expression of miR-587 and its target gene Wnt5β. Overexpression of miR-587 blocked the inhibitory effect of RP11-142A22.4 on preadipocyte differentiation. Moreover, the downregulation of miR-587 restored preadipocyte differentiation upon inhibition by RP11-142A22.4 silencing. Our results suggest that RP11-142A22.4 can control adipocyte differentiation via the miR-587/Wnt5β signaling pathway and serve as a potential target for obesity treatments.
Highlights
Obesity has emerged as an epidemic and has become an unprecedented public health challenge
Expression profile of long noncoding RNAs (lncRNAs) in visceral adipose tissue (VAT) We identified 331 lncRNAs with significantly differential expression in VAT between lean and obese people (P < 0.05)
The results show that RP11-142A22.4 and miR-587 were both enriched in the examined preadipocytes (Fig. 4b and Supplementary Fig. 6)
Summary
Obesity has emerged as an epidemic and has become an unprecedented public health challenge. Previous studies have suggested that an increase in adipose tissue is the main cause of obesity and the associated complications[1,2]. To understand the functional mechanisms of obesity, it is necessary to study the adipose tissue of obese people. Many crucial obesity-associated genes have been discovered[3], but their exact functional. We profiled the lncRNA expression patterns in visceral adipose tissue (VAT) of lean people and obese people and found that lncRNA RP11-142A22.4 is the most highly upregulated lncRNA in obese people compared with lean people. Official journal of the Cell Death Differentiation Association. Zhang et al Cell Death and Disease (2020)11:475 expression. Our results imply that RP11142A22.4 plays a crucial role in adipogenesis and could serve as a potential therapeutic target for obesity treatment
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