Hedgehog信号在胶质瘤中激活，但缺乏明确的调控机制。课题组前期发现SHH、SMO和GLI1等在胶质瘤中激活；生物信息学分析SMO的3`UTR有miR-328结合位点；miR-328的表达与SMO负相关；上调miR-328抑制SMO表达及Hedgehog信号通路的转录活性。因此我们提出科学假说"miR-328/SMO/GLI1解析脑胶质瘤中hedgehog信号通路异常激活的新机制"。本课题拟建立miR-328不同表达状态细胞模型,应用荧光素酶实验验证SMO是miR-328的靶点，western blot检测miR-328对hedgehog下游因子的影响；进一步拟体内外功能实验验证miR-328对胶质瘤生物学行为的影响；大规模病例探究miR-328与信号通路关键节点在胶质瘤诊断和预后中的指导作用。本研究可为明确胶质瘤中hedgehog信号通路异常激活的新机制，为胶质瘤靶向治疗提供新依据。

Although aberrant activation of hedgehog signaling pathway has been observed in gliomas, the explicit regulatory mechanisms remain to be elucidated. The preliminary researches of our group demonstrated that SHH, SMO and GLI1, which are key components implicated in hedgehog signaling, were activated. Bioinformatics analysis revealed the existence of miR-328 binding site in SMO 3`UTR. The expression of miR-328 was negatively correlated with SMO. Meanwhile up-regulation of miR-328 inhibited SMO expression and hedgehog signaling transcriptional activity. Thus, we propose a scientific hypothesis that miR-328/SMO/GLI1 is a novel mechanism which could explain the aberrant activation of hedgehog signaling in gliomas. This research will establish glioma cell models with different states of miR-328 expression and use luciferase assay and western blot to confirm that SMO is a direct target of miR-328 and the effect of miR-328 on hedgehog signaling downstream factors. Further experiments in vitro and vivo are needed to verify the influence of miR-328 on gliomas biological behaviors. And Large-scale clinical cases are also needed to elucidate the predictive function of miR-328 and key moleculars of hedgehog signaling in gloma diagnosis and prognosis. Our research will provide a novel mechanism to expound abnormal activation of hedgehog signaling and a novel approach for clinical gliomas targeted therapies.