hsa-miR-378的生物信息学特征及其在人脂肪细胞中的表达调控规律

发布时间：2019-04-21 09:37

【摘要】：目的本研究主要探讨：1、脂肪细胞分化相关micro-RNA-hsa-miR-378的预期生物学功能,包括转录调控、靶基因功能；2、miR-378在脂肪细胞分化前后的表达变化。3, TNF-α、IL-6、leptin、resistin分别对人脂肪细胞中miR-378表达的影响。方法1、应用UCSC Genome Browser Promoter scan等在线工具,分析hsa-miR-378在基因组上下游10kb以内的CpG岛分布情况、转录起始位置(TSS)、转录因子结合位置(TFBS)等；选择TargetScan、PicTar、MiRanda三种计算方法预测hsa-miR-378的靶基因,取三个预测结果的交集,并合并DIANA LAB-TarBase6.0数据库的已验证靶标,对所得靶基因集分别进行GO注释描述、GO富集分析和pathway富集分析。2、利用Real-time PCR技术,检测脂肪细胞分化前后miR-378的表达水平,及TNF-α、IL-6等干预前后miR-378的表达水平。结果1、生物信息学分析显示：hsa-miR-378可能具有独立的启动子,可能受C/EBP β转录因子的调控；其预测靶基因集合富集于转录调控、蛋白质修饰、细胞分化等生物学过程和功能(P0.01)；并显著富集于TGF-β信号通路、Wm信号通路等4个信号通路,以及甲状腺癌、系统性红斑狼疮等8个疾病通路中p0.05)。2、分化成熟的人脂肪细胞中miR-378的表达量较分化前显著上调(P0.05)。3、TNF-α、IL-6及leptin显著上调人成熟脂肪细胞中miR-378的表达(P0.05),但resistin对其表达量无影响(P0.05)。结论hsa-miR-378与人脂肪细胞的分化成熟过程密切相关；m1K-3/8可能生肥胖及其并发症的发生发展中起重要作用,并为肥胖的早期干预及肥胖相关并发症的防治提供新的靶点。
[Abstract]:Objective to investigate the expected biological functions of adipocyte differentiation-related micro-RNA-hsa-miR-378, including transcriptional regulation and target gene function. 2. The changes of miR-378 expression in adipocytes before and after adipocyte differentiation. 3. The effects of TNF- 伪 and IL-6,leptin,resistin on the expression of miR-378 in human adipocytes. Methods 1. UCSC Genome Browser Promoter scan and other online tools were used to analyze the distribution of CpG islands within the upstream and downstream 10kb of the genome, and the transcription initiation site, (TSS), transcription factor binding site (TFBS), and so on. Three calculation methods of TargetScan,PicTar,MiRanda were used to predict the target gene of hsa-miR-378. The intersection of the three prediction results was taken, and the validated target of DIANA LAB-TarBase6.0 database was combined. The target gene set was described by GO annotation. GO enrichment analysis and pathway enrichment analysis. 2. MiR-378 expression level before and after adipocyte differentiation and miR-378 expression level before and after intervention of TNF- 伪 and IL-6 were detected by Real-time PCR technique. Results 1. Bioinformatics analysis showed that hsa-miR-378 may have independent promoter and may be regulated by C/EBP 尾 transcription factor. The predicted target genes were enriched in biological processes and functions such as transcriptional regulation, protein modification, cell differentiation and so on (P0.01). And significantly enriched in TGF- 尾 signaling pathway, Wm signaling pathway, and 8 disease pathways, such as thyroid cancer and systemic lupus erythematosus (p0.05). The expression of miR-378 in differentiated and mature human adipocytes was significantly up-regulated compared with that before differentiation (P0.05). 3. TNF-伪, IL-6 and leptin up-regulated the expression of miR-378 in human mature adipocytes (P0.05). However, resistin had no effect on its expression (P0.05). Conclusion hsa-miR-378 is closely related to the differentiation and maturation of human adipocytes. M1K-3/8 may play an important role in the occurrence and development of obesity and its complications, and provide a new target for the early intervention of obesity and the prevention and treatment of obesity-related complications.
【学位授予单位】：南通大学
【学位级别】：硕士
【学位授予年份】：2013
【分类号】：R723.14

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