我们前期利用miRNA芯片及体外实验筛选出miR-1182为胶质瘤候选抑癌miRNA，但其在胶质瘤中的确切功能及调控机制尚未见报道。根据前期研究和预实验结果，我们推测SIP1结合miR-1182启动子区域抑制miR-1182的表达，而miR-1182可能分别与Myc和NFκB形成反馈回路抑制PI3K/Akt信号通路，逆转由SIP1导致的胶质瘤恶性表型。本项目拟利用转基因技术、ChIP、EMSA、荧光素酶报告系统、体内外功能实验，旨在确证miR-1182在胶质瘤中的抑癌功能；证实SIP1负性调控miR-1182的表达并激活PI3K/Akt通路促进胶质瘤恶性表型；揭示miR-1182分别与Myc和NFκB形成的反馈回路调控机制。由此将能够证实miR-1182作为抑癌miRNA，是SIP1的作用靶点，为阐明胶质瘤发病分子机理提供一个新的思路，并为逆转SIP1导致的胶质瘤恶性表型提供新的药物靶点。

Our previous studies with miRNA array and cell lines showed that miR-1182 was an anti-oncogene miRNA for glioma. However, the detailed role and molecular mechanism of miR-1182 in glioma still unknown. Based on the bioinformatic analyses and preliminary experiments, we proposed that miR-1182 reverses the malignant phenotype of SIP1(Smad interacting protein-1) by feedback inhibition of Myc and NFκB expression through regulating PI3K/Akt pathway in glioma. To validate this mechanism, gene transfection, ChIP, EMSA, luciferase reporter system, in vivo and in vitro functional test assays will be performed to: Confirm the role of tumor inhibitor of miR-1182 in glioma. Validate SIP1 as a transcription factor mediates glioma cell proliferation and invasion progress by inhibiting the miR-1182 expression through directly regulating its promoter, which induce the PI3K/Akt pathway in glioma. Verify that the promoter region of miR-1182 contains Myc and NFκB binding sites and both Myc and NFκB were direct targets of miR-1182, which forms a feedback loop to regulate the PI3K/Akt pathway mediated by SIP1 in glioma. We anticipate that our results will provide that miR-1182 as a target of SIP1 is antimiRNA, and verify a new insight to the molecular mechanisms for glioma, and so be helpful for identifying potential target candidates on therapeutic intervention of malignant phenptype mediated by SIP1 in glioma.