miR-382在小鼠腭板发生过程中的作用机制研究

发布时间：2018-05-02 13:02

本文选题：miR-382 + Porcn　；参考：《杭州师范大学》2015年硕士论文

【摘要】：唇腭裂是哺乳动物类先天性遗传病之一,在我国每700人中就有1人患有此病,属高发病。目前,公认的致病机制有有两方面环境因素和遗传因素,大多数的唇腭裂是由遗传因素导致。例如,Sox11基因的突变导致小鼠舌头异常进而使得腭板不能正常发育,以至导致唇/腭裂的产生。因此,阐明唇腭裂的发病机制将会促进唇腭裂的诊断和修复。哺乳动物类的腭板发育进程受到严格的分子调控,包括细胞增殖、凋亡、迁移以及细胞类型的转化等。在腭板融合时期涉及到腭板间充质细胞的增殖凋亡及迁移,某些基因翻译活性受抑制,这时期mRNA翻译活性受到抑制主要是转录后调控机制调控,而大部分基因转录后翻译抑制受microRNA调控。我们研究组已验证miR-382在小鼠融合时期表达量显著下调,本论文的目的就是要阐明miR-382在小鼠腭板发育过程中分子机制。我们研究发现当miR-382在腭板间充质细胞过表达后,Porcn蛋白表达明显下调,通过抑制Porcn(Porcupine)介导促进细胞的迁移,导致下游基因经典Wnt通路家族基因如Wnt1、Wnt3和Wnt6等的下调。miR-382异常表达可能导致腭板发育异常。综上所述,miR-382通过调控porcn基因调节经典Wnt通路家族基因的表达,进一步影响细胞的功能。
[Abstract]:Cleft lip and palate is one of the congenital diseases in mammals. At present, there are two kinds of environmental factors and genetic factors, and most of cleft lip and palate are caused by genetic factors. For example, the mutation of Sox11 gene leads to abnormal tongue in mice and leads to abnormal development of palatal plate, leading to lip / cleft palate. Therefore, to clarify the pathogenesis of cleft lip and palate will promote the diagnosis and repair of cleft lip and palate. The development of palatal plate in mammals is regulated by strict molecular regulation, including cell proliferation, apoptosis, migration and cell type transformation. The proliferation, apoptosis and migration of mesenchymal cells in palatine lamina were involved in palatine lamina fusion, and some gene translation activities were inhibited. During this period, the inhibition of mRNA translation activity was mainly regulated by posttranscriptional regulation mechanism. However, most of the gene posttranscriptional inhibition is regulated by microRNA. Our team has demonstrated that the expression of miR-382 is significantly down-regulated during fusion in mice. The aim of this paper is to elucidate the molecular mechanism of miR-382 during the development of palatal plate in mice. We found that the expression of miR-382 protein was down-regulated after overexpression of miR-382 in mesenchymal cells of palatal plate, and promoted cell migration by inhibiting Porcupine. The down-regulation of down-regulated .miR-382 genes in the classical Wnt pathway family of downstream genes, such as Wnt1, Wnt3 and Wnt6, may lead to abnormal palatine plate development. In conclusion, miR-382 regulates the expression of classical Wnt family genes by regulating porcn gene, and further affects cell function.
【学位授予单位】：杭州师范大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：S858.91

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