功能未知的miR-1268调节人脂肪细胞分化的机制研究

The expression of miR-1268 was significantly decreased in fully differentiated human adipocyte via miRNA microarray screening. Our following study showed that: 1) Overexpression of miR-1268 significantly inhibited adipogenesis. 2) HELZ2, a critical regulator of adipogenesis, is a direct target of miR-1268 by bioinformatic analysis and dual luciferase reporter assay. 3) There were negative correlation between miR-1268 and HELZ2 expression in adipogenesis and omental adipose tissues of normal weight and obese subjects. These results indicated that the mechanism of miR-1268 involved in adipogenesis might be related to HELZ2 in the PPARγ pathway. In this study, we will investigate the effect of miR-1268 on adipogenesis. Furthermore, we will explore the mechanism of miR-1268 on adipogenesis by overexpression and slience techniques. Finally, we will evaluate the relationship between miR-1268, HELZ2 and BMI, serum lipid. This study may provide a new intervention target for obesity.

脂肪细胞分化异常是肥胖发生发展的细胞生物学基础。MiR-1268是我们采用μParaflo®微流体芯片技术发现的一条在诱导分化成熟脂肪细胞中低表达的、功能未知的miRNA。前期研究发现，过表达miR-1268可显著抑制脂肪细胞分化；PPARγ共调节因子HELZ2为miR-1268的直接靶基因；在脂肪细胞分化前后以及网膜脂肪组织中，miR-1268与HELZ2表达趋势均呈负相关。上述实验结果提示miR-1268可能通过抑制HELZ2参与PPARγ信号通路调节脂肪细胞分化进程。本研究拟：系统评价miR-1268对脂肪细胞分化的影响；采用挽救实验，系统论证 miR-1268 影响脂肪细胞分化的分子机制；评估脂肪组织中miR-1268和HELZ2表达与BMI、血脂之间的关系。鉴于miR-1268与脂肪细胞分化机制未见报道，所以本研究具有源头创新性，很可能为肥胖的药物研发提供新靶点。

脂肪细胞分化异常是肥胖发生发展的细胞生物学基础。MiR-1268是我们采用μParaflo®微流体芯片技术发现的一条在诱导分化成熟脂肪细胞中低表达的、功能未知miRNA。前期研究发现，过表达miR-1268可显著抑制脂肪细胞分化；PPARγ共调节因子HELZ2为miR-1268的直接靶基因；在脂肪细胞分化前后以及网膜脂肪组织中，miR-1268与HELZ2表达趋势均呈负相关。上述实验结果提示miR-1268可能通过抑制HELZ2参与PPARγ信号通路调节脂肪细胞分化进程。本研究中，我们发现miR-1268沉默可显著促进脂肪细胞分化；挽救实验进一步证实miR-1268通过调控HELZ2影响脂肪细胞分化进程；在人脂肪组织中miR-1268与BMI呈逆相关而HELZ2于BMI呈正相关。因此，本研究阐明miR-1268参与脂肪细胞分化调节机制，很可能为肥胖的药物研发提供新靶点。