TXLNA调控上皮间充质转化（EMT）促进胶质瘤侵袭进展的机制研究

Gliomas represent the most common primary malignant brain tumors. Despite current aggressive treatments, almost all gliomas can relapse within a short course. Previously, multiomics technologies were applied to find a glioma associated gene TXLNA, which could significantly promote tumor cell invasion and migration but not proliferation in later cytological experiments. Additionally, TXLNA also showed the ability to interact with STRAP and affect epithelial-mesenchymal transition (EMT) in glioma. As demonstrated, EMT accounts for the invasion and migration of epithelial cancer cells and contributes to therapeutic resistance and tumor recurrence. Targeting EMT could be key to improving clinical out of glioma patients. On the basis, we will utilize several methods and technologies including protein mass spectrometry, Co-IP, nude mouse transplantation tumor experiment, luciferase assay, dual luciferase assay, CHIP-PCR, next-generation sequencing, bioinformatics analysis, ect further study the function and the mechanism of TXLNA on modulating EMT, which is intended to provide a theoretical evidence in developing therapeutic strategies targeting TXLNA pathway and improving prognosis of glioma patients.

脑胶质瘤是中枢神经系统最常见的原发恶性肿瘤，治疗困难，患者不可避免面临肿瘤复发。申请人前期利用多组学数据分析筛选出胶质瘤潜在相关基因TXLNA，并在细胞功能学实验中发现TXLNA可显著提升肿瘤侵袭迁移能力，但对增殖促进不明显，同时TXLNA存在与STRAP互作可能，两者均与EMT密切相关。研究显示EMT是上皮源性恶性肿瘤细胞获得迁移侵袭能力的重要生物学过程，是肿瘤治疗抵抗和复发进展的根本原因。针对EMT核心调控因素的治疗，可能是提高胶质瘤治疗疗效的关键。在此基础上，拟利用蛋白质谱、免疫共沉淀、细胞亚定位、裸鼠原位成瘤、双荧光报告素酶、染色质共沉淀、转录组测序、生物信息学分析等技术和方法，进一步明确TXLNA对胶质瘤EMT的调控作用，探索TXLNA通过与STRAP互作调控EMT促进肿瘤进展的分子机制，揭示靶向TXLNA信号通路治疗胶质瘤的临床转化潜能，为提高胶质瘤患者预后提供实验和理论依据。

脑胶质瘤是最常见的神经系统恶性肿瘤，具有侵袭性生长特性，手术难以全切，极易复发，现有治疗方式一直缺乏突破性进展，阐明脑胶质瘤侵袭进展的分子机理，开拓新干预靶点是该领域非常迫切的前沿课题。课题组利用胶质瘤数据库结合大样本芯片分析，发现TXLNA表达与胶质瘤恶性程度密切相关，是患者临床预后的独立危险因素。进一步通过细胞功能学实验证实TXLNA可显著提升肿瘤侵袭迁移能力，促进上皮-间充质转化（EMT），抑制TXLNA可显著延长荷瘤小鼠生存时间。研究显示EMT是上皮源性恶性肿瘤细胞获得迁移侵袭能力的重要生物学过程，是肿瘤治疗抵抗和复发进展的根本原因。在此基础上，项目利用蛋白质谱、免疫荧光亚定位、双荧光报告素酶、染色质共沉淀、生物信息学分析等技术和方法，探索了TXLNA在胶质瘤侵袭进展中的分子通路，阐明了SP1作为TXLNA上游调控因子的作用机制，揭示靶向TXLNA信号通路治疗胶质瘤的临床转化潜能，为提高胶质瘤患者预后提供实验和理论依据。