多形性胶质母细胞瘤(Glioblastoma multiforme,GBM)是最常见的恶性人类脑肿瘤，影响其预后的主要临床因素为病人确诊年龄，术前卡氏评分和辅助治疗等。最新研究表明，microRNAs在GBM的恶性进程中扮演着重要的角色。本课题组通过前期的大样本基因组学数据挖掘，建立了一个整合mRNAs和microRNAs的GBM分子预后模型,发现miR-148a和DLGAP1在GBM中分别呈现明显的高表达和低表达并与病人的生存相关，生物信息学预测及初步试验表明与GBM增殖和侵袭转移相关的DLGAP1很可能是miR-148a的一个靶基因。我们拟进一步运用体内外实验技术，从细胞功能，动物模型及结合临床病例来探讨miR-148a靶向调控DLGAP1促GBM细胞增殖和侵袭转移的机制，为应用miR-148a作为GBM新的诊断标记和治疗靶点提供有力的科学依据。

Glioblastoma multiforme (GBM) is the most common and lethal type of primary brain tumor in adults. Clinical variables such as patient age at diagnosis, preoperative Karnofsky performance score, and adjuvant therapy etc.are predictive of the overall survival of patients with GBM. Resent studies have shown that, microRNAs paly an important role in the malignant process of GBM. We build a molecular model for GBM prognosis by integrating mRNAs and microRNAs expression data and found that the up-regulated expressions of miR-148a and down-regulated expression of DLGAP1 were correlated with patient survival significantly. DLGAP1,which is involved in cell proliferation and metastasis of GBM ,is a potential target of miR-148a in GBM by bioinformatic prediction and primary experiments. In this project, we will use in vitro and in vivo experiment technology to investigate the role of miR-148a and its target regulation of DLGAP1 in GBM proliferation,invasion and matastasis from three level of cell function, animal model, and clinical cases. This promotes understanding of GBM pathogenesis and provides scientific evidences for miR-148a as a new dianostic marker and therapeutic target for GBM.