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.

新兴证据表明，较长的非编码RNA（lncRNA）在基因表达的调控中起着至关重要的作用。然而，lncRNAs对脂肪形成的功能性贡献仍在很大程度上未被探索。在这项研究中，我们调查了内脏脂肪组织中lncRNAs表达模式的总体变化，并将RP11-142A22.4确定为显着上调的lncRNA。在分离的前脂肪细胞中，敲低RP11-142A22.4抑制分化并降低C /EBP-α和PPAR-γ表达。对潜在机制的研究表明，RP11-142A22.4包含功能性miR-587结合位点。如萤光素酶报告基因测定所示，miR-587中RP11-142A22.4结合位点的突变消除了相互作用。此外，RP11-142A22.4影响了miR-587及其靶基因Wnt5β的表达。miR-587的过表达阻断了RP11-142A22.4对前脂肪细胞分化的抑制作用。此外，miR-587的下调在受到RP11-142A22.4沉默抑制后恢复了前脂肪细胞的分化。我们的结果表明，RP11-142A22.4可以通过miR-587 /Wnt5β信号通路控制脂肪细胞的分化，并可以作为肥胖症治疗的潜在靶标。