脂代谢相关基因烷基甘油酮磷酸核酶受Tudor-SN调控影响人神经胶质瘤增殖和侵袭的机制研究

肿瘤发生发展与脂代谢之间关系密切，醚脂合成关键酶—烷基甘油酮磷酸核酶（AGPS）在多种恶性肿瘤中高表达，并在肿瘤过程中发挥重要作用，被认为是联接脂代谢和肿瘤的桥梁，其机制尚不清晰。我们前期发现shRNA敲除或抑制剂抑制神经胶质瘤细胞AGPS表达，均可抑制肿瘤增殖和侵袭，增强肿瘤药物敏感性，调节肿瘤相关基因表达，已发表多篇SCI论文。我们认为AGPS与神经胶质瘤恶性程度及患者预后密切相关，具有临床转化价值。我们通过病理标本发现AGPS和另一种脂代谢相关癌基因Tudor-SN均在神经胶质瘤组织中高表达，且均与肿瘤级别呈正相关。本项目拟在此基础上通过体外实验，验证AGPS对神经胶质瘤增殖与侵袭等恶性表型的调控作用和机制，论证AGPS经Tudor-SN通过NF-κB和（或）miR-127间接调节其在肿瘤中表达的假设并鉴定分子间相互作用的精细模式，探索AGPS作用的靶点和信号通路。

There was a closely relationship with tumor process and lipid metabolism, and alkylglycerone phosphate synthase (AGPS) which was the key enzyme of ether lipid considered the bridge of lipid metabolism and tumor, improved expression in malignant tumors and played an important role in the proliferation and invasion of tumors, but the mechanism is not cleared. Our previous found that AGPS silencing by shRNA or AGPS inhibition by inhibitor could suppress the proliferation and invasion potential, improve the drug sensitivity and regulate the expression of tumor related gene in gliomas and reported by some SCI papers. It was considered there was closely relationship with gliomas malignancy and patient prognosis, and had clinical transformation value. We also found that there was a highly expression of both of AGPS andTudor-SN which was another lipid metabolism related oncogene in human gliomas tissues and positive correlation with tumor grade by pathological report, The object of this study is to observe the effects and mechanism of AGPS on the potential of proliferation and invasion in gliomas cells, demonstrate the hypotheses that Tudor-SN might indirectly affect the expression of AGPS through NF-κB and (or) miR-127 in gliomas cells and its subtle model of molecules interaction, explore target points and signal pathway of AGPS by in vitro study.