一个新克隆的microRNA在甲状旁腺发育及甲状旁腺腺瘤发病中的作用及机制研究

项目名称： 一个新克隆的microRNA在甲状旁腺发育及甲状旁腺腺瘤发病中的作用及机制研究

项目编号： No.81471008

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 张红

作者单位： 中南大学

项目金额： 73万元

中文摘要： 我们首次克隆了一个新的甲状旁腺特异性表达的miRNA（暂命名为miR-A），其在胚胎早期及出生后甲状旁腺表达下降，而在胚胎中晚期及甲状旁腺瘤中高丰度表达。故推测miR-A与胚胎中晚期甲状旁腺分化发育及高分化甲状旁腺瘤发病相关。本课题拟证实此设想。首先诱导甲状旁腺前体细胞向成熟细胞分化，在此过程中运用基因转染策略调控miR-A表达，观察miR-A表达改变对甲状旁腺细胞分化的影响，并验证ZEB1为miR-A靶基因，阐明miR-A在甲状旁腺细胞分化过程中的作用。在体内，用agomirs/antagomirs干预不同胚胎期小鼠，构建miR-A过表达或缺失动物模型，解析miR-A在甲状旁腺发育中的作用。进而在NOD/SCID鼠甲状旁腺瘤模型中促进或抑制miR-A表达，探讨miR-A在高分化腺瘤发生中的机制。本研究有利于阐明甲状旁腺发育机理，为甲状旁腺瘤的防治拓展新思路。

中文关键词： 微小RNA；甲状旁腺；甲状旁腺腺瘤；ZEB-1；发育

英文摘要： We cloned a novel tissue specific expressing miRNA(temporarily named miR-A) in parathyroid gland in early and middle embryo. The exprssion of miR-A decreased in early embryo and postnatal, whereas miR-A was highly expressed in parathyroid adenoma. Therefore, we speculated that miR-A promoted the development of parathyroid gland in early and middle embryo. Moreover it was associated with the mechanism of development of parathyroid adenoma. The aim of our study is to prove this hypothesis. First, we induce the parathyroid precursor cells to form mature cells by culture mediums without calcium which are consist of serum. During this stage, by regulating the expression of miR-A through gene transfection strategy, we observe the changes in parathyroid cells differentiation and verify the target gene of miR-A is ZEB1 and further clarify the function of miR-A in parathyroid cells differentiation. Second, in order to analyze the function of miR-A in parathyroid development and discuss if highly expressed miR-A result in ZEB1 down-regulating which help to reveal the mechanism of onset of parathyroid adenoma, we construct over/low-expressed miR-A animal models in different stages by interfering different embryo stages and postnatal mice with agomirs/antagomirs. This research contribute to clarify the mechanism of parathyroid development and enable to find preclusive and therapeutic approaches for the parathyroid adenoma.

英文关键词： microRNA;parathyroid;parathyroid adenoma;ZEB-1;development