miR-133b可能通过调控foxO1的表达影响小鼠B细胞发育  

miR-133b May Regulate Mouse B Cell Development by Targeting The Transcription Factor foxO1

作　　者：梁婧文[1] 王鹏[1] 陈黎[1] 胡益清[1] 孙亿[1] 

机构地区：[1]中国农业大学农业生物技术国家重点实验室,北京100193

出　　处：《生物化学与生物物理进展》2011年第8期744-750,共7页Progress In Biochemistry and Biophysics

基　　金：国家重点基础研究发展计划资助项目(973)(2010CB945300)~~

摘　　要：microRNAs(miRNAs)是一类具有转录后调控作用的非编码RNA,在发育、细胞增殖、凋亡及肿瘤发生等多种生理和病理过程中发挥重要作用.为全面了解小鼠B细胞中miRNAs的表达模式,利用流式细胞仪(FACS)分选处于不同发育时期的B细胞,采用TaqMan誖低密度芯片对其进行检测,筛选到pre-B阶段9个miRNAs表达量显著上调.将筛选出的miRNAs进行靶基因预测,并对预测靶基因进行功能聚类和通路分析,发现约4%的基因参与免疫系统过程,包括Bcl2、Kit等.选取foxO1与miR-19b、miR-142-3p、miR-106b、miR-182及miR-133b进行初步功能验证,双荧光素酶报告系统及Westernblot检测结果均显示,miR-133b可直接作用于foxO1 3′UTR从而降低foxO1的表达.结合人类和小鼠B细胞中foxO1的表达情况分析,其表达模式同miR-133b表达模式呈负相关,说明miR-133b可能参与了B细胞发育过程中foxO1的表达调控过程.MicroRNAs（miRNAs） are a class of small non-coding RNAs that regulate gene expression at post-transcriptional level.They play important roles in multiple physiological and pathological processes,including development,cell proliferation,apoptosis,metabolism and tumorigenesis,etc.Mouse B cell at different development stages were isolated by FACS and analyzed the miRNAs profile using TaqMan Low Density Array.The data showed that 9 miRNAs were significantly up-regulated in the pre-B cells.Functional clustering and pathway analysis of 1102 predicted target genes of these miRNAs showed that about 4% of the genes involved in immune system processes,including Bcl2,Kit,etc.A dual luciferase reporter system and Western blot were used to validate the interaction between foxO1 and miR-19b,miR-142-3p,miR-106b,miR-182,miR-133b.The results show that miR-133b can directly regulate the expression of foxO1.According to the foxO1 expression profile of human and mouse,the expression pattern is negatively correlated with that of miR-133b,indicating that miR-133b may be involved in the regulation of foxO1 in B cell development.

关 键 词：B细胞发育 MICRORNAS miR-133b FOXO1 

分 类 号：Q78[生物学—分子生物学] R392[医药卫生—免疫学]