miR-17-92基因簇对胰腺祖细胞增殖分化的调控研究

项目名称： miR-17-92基因簇对胰腺祖细胞增殖分化的调控研究

项目编号： No.31272520

项目类型： 面上项目

立项/批准年度： 2013

项目学科： 农业科学

项目作者： 滕春波

作者单位： 东北林业大学

项目金额： 80万元

中文摘要： 胰岛β细胞缺失或功能发生障碍将引起动物和人类糖尿病，探索胰腺祖细胞增殖和定向分化为β细胞的机制可为糖尿病治疗提供线索。在前期工作中，我们筛选到胰腺祖细胞增殖分化转换过程中差异表达的miR-17-92基因簇miRNAs，其成员在胰腺祖细胞中能靶向作用于β细胞分化关键转录因子。本课题拟对miR-17-92基因簇成员在胚胎和成体胰腺中的表达进行全面分析；通过在胰腺祖细胞中过表达和抑制各成员miRNAs，研究它们对胰腺祖细胞增殖和分化的影响；通过生物信息学预测、过表达miRNA后基因表达变化分析、双荧光素酶报告实验和Western blot等手段研究17-92基因簇成员对胰腺祖细胞的作用机制；通过分析miR-17-92基因簇与胰腺发育关键转录因子、miR-375等小RNA的调控关系，进一步探索miR-17-92基因簇miRNAs对胰腺祖细胞的调控机理，为利用胰腺祖细胞及小RNA治疗糖尿病打下基础。

中文关键词： miR-17-92基因簇；胰腺祖细胞；增殖；分化；机制

英文摘要： Loss or dysfunction of insular β cells will cause animal and human diabetes. Exploration of the mechanisms which control the proliferation of pancreatic progenitors and their differentiation into β cells can provide clues for diabetes treatment. In previous study, we have found that miR-17-92 cluster miRNAs are differentially expressed on the transition of the pancreatic progenitor cells from proliferation to differentiation, and these miRNAs can target key transcription factors in β-cell differentiation. This subject will completely analyze the expression of miR-17-92 cluster miRNAs in embryonic and adult pancreas, and explore the effects of miR-17-92 cluster miRNAs on the proliferation and differentiation of pancreatic progenitor cells through overexpression or inhibition of them in the pancreatic progenitor cells. Through the bioinformatic forecast, gene expression analysis, and dual luciferase report assays, the target genes of miR-17-92 cluster miRNAs in pancreatic progenitor cells will be searched. Moreover, the relationship among miR-17-92 cluster miRNAs, key transcription factors during pancreatic development, and other small RNAs, such as miR-375, will be further explored. We expected to discover the regulatory mechanisms of miR-17-92 cluster miRNAs on pancreatic progenitor cells, and lay the foundation

英文关键词： miR-17-92 cluster miRNAs；pancreatic progenitor cells；proliferation；differentiation；mechanism