miR-31在髓母细胞瘤发生过程中的作用以及机制研究

髓母细胞瘤（Medulloblastoma, MB）的发生与Sonic Hedgehog （Shh）通路激活密切相关。在Shh受体Patched (Ptch) 缺陷的人和小鼠中， Shh通路异常激活，导致MB高发。近年关于小RNA（miRNA）的研究表明，一些miRNAs也与MB有重要关系。但MB中Shh通路相关miRNAs的研究尚非常有限。本课题组通过深度测序筛选Ptch单倍体缺失小鼠MB中差异表达的miRNAs，以阐明该MB中miRNAs的作用。结果显示，miR-31在该MB中显著低表达，并在人MB细胞系DAOY中有基因水平缺失，而且过表达miR-31抑制DAOY成瘤性。本研究将深入探讨miR-31抑制该MB的分子机制，为该MB的临床诊断及治疗提供新的思路。本研究包含两方面：1.寻找miR-31的靶基因。2. 阐明miR-31对该MB的作用机理。

Medulloblastoma (MB) is closely related with the activation of Sonic Hedgehog (Shh) pathway. Deficiency of Shh receptor Patched (Ptch) in human and mouse leads to highly activated Shh signaling, resulting in the elevated occurrence of MB. Recently, more and more studies on miRNAs suggest that some miRNAs are also involved in MB, but specific miRNAs in Shh-MB are barely investigated. In order to find the role of miRNAs in the MB caused by Ptch deficiency, we compared the profile of miRNAs in the MB from Ptch+/- mice with that in the normal cerebellum by deep sequencing. Our results showed that miR-31 was dramatically decreased in the MB, and miR-31 gene was deleted in a human MB cell line DAOY. Additionally，over expression of miR-31 in DAOY cells reduced their ability to form tumors. So we are going to further examine the role of miR-31 in Shh-MB and the molecular mechanism involved. This study will help to understand the role of miRNAs in Shh-MB, and provide new possible therapies for this type of MB.