miR-144/451基因簇调控网络的生物信息学分析  

Bioinformatic analysis of the miR-144/451 cluster mediated regulation network

作　　者：聂伟伟[1] 唐林[1] 韦凤[1] 陈龙邦[1] 张辰宇[2] 朱琳 李冬海[2] 管晓翔[1] 

机构地区：[1]南京大学医学院临床学院(南京军区南京总医院)肿瘤内科,南京210002 [2]南京大学生命科学院医药生物技术重点实验室,江苏省小核糖核酸工程研究中心,南京210093 [3]南京市先声药业研究院生物评价研究所,南京210042

出　　处：《医学研究生学报》2012年第3期229-233,共5页Journal of Medical Postgraduates

基　　金：国家自然科学基金(81141094,31000323);江苏省自然科学基金(BK2011656);高等学校博士学科点专项科研基金(20100091120023,20100091120026);高校基本科研业务费专项资金(1095020823)

摘　　要：目的生物信息学方法是预测miRNA二级结构及miRNA靶基因的有用工具。miRNA、转录因子和靶基因之间的调控网络参与多种生理、病理活动的分子机制。文中用生物信息学方法预测mir-144/451基因簇的调控网络结构。方法运用多个在线数据库,研究miR-144/451基因簇的上游转录因子及下游靶基因间的多个反馈和前反馈环路,对参与miR-144/451基因簇调控环路的基因进行功能聚类分析,绘制miR-144/451基因簇的核心调控网络图。结果 miR-144/451基因簇与其上游转录因子GATA1有17个共调控的靶基因,与生物体蛋白磷酸化、性腺发育、上皮细胞分化、葡萄糖代谢等生化学过程密切相关,并参与胰岛素信号通路、哺乳动物雷帕霉素靶蛋白(mammalian target of rapamycin,mTOR)信号通路、血管内皮生长因子(vascular endothelial growth factor,VEGF)信号通路、自然杀伤细胞介导的细胞毒作用、Toll样受体信号通路、ErbB信号通路及黄体酮调节卵细胞成熟等体内重要生理过程。结论对miR-144/451基因簇调控网络的生物信息学分析有助于理解其在细胞发育、细胞周期调控和肿瘤发生过程中的作用机制,为后续实验提供了理论依据。Objective Bioinformatic methods are useful tools for predicting the secondary structure and target gene of miRNA.The regulation network of miRNAs,transcription factors and target genes is involved in molecular mechanisms of physiological and pathological activities.This study is to predict the miR-144/451 cluster regulation network using online bioinformatic tools.Methods We studied some of the feedforward and feedback loops by integrating compressive information from different online databases.After function analysis of the genes involved in the circuits regulated by the miR-144/451 cluster,we determined the regulation network of the gene cluster.Results There were 17 joint targets of the miR-144/451 cluster and its upstream transcriptional factor GATA1,which played important roles in such biological processes as protein amino acid phosphorylation,gonad development,epithelial cell differentiation and glucose metabolism,as well as in some important signaling pathways,including insulin signaling pathway,mTOR signaling pathway,VEGF signaling pathway,natural killer cell mediated cytotoxicity,progesterone-mediated oocyte maturation,Toll-like receptor signaling pathway,and ErbB signaling pathway.Conclusion Bioinformatic analysis of the regulation network of the miR-144/451 cluster potentially provide a good guideline for deeper insights into its mechanisms of regulating cell development and tumorigenesis.

关 键 词：微小RNA miR-144/451基因簇 生物信息学 反馈环路 基因功能 

分 类 号：Q522[生物学—生物化学]