外泌体作为细胞间通讯的关键介质，为肿瘤耐药研究提供了新的模式，也有望成为新型诊断标志物和治疗工具。我们前期发现：微小RNA，miR-151a在胶质瘤替莫唑胺耐药细胞及其外泌体中低表达；携带低表达miR-151a的耐药细胞外泌体进入受体细胞，可能通过miR-151a对XRCC4与ATM蛋白的靶向作用，促使受体细胞耐药表型增强。为此本课题拟明确miR-151a靶向 XRCC4和ATM蛋白调控DNA双链断裂修复途径NHEJ和HR通路的过程，解析外泌体介导的miR-151a调控替莫唑胺耐药机制，探索包裹miR-151a的外泌体逆转替莫唑胺耐药的作用，分析循环中外泌体相关miR-151a临床价值。本研究可确立胶质瘤耐药细胞外泌体传递miR-151a通过序贯调控受体细胞中DNA双链断裂修复途径（NHEJ和HR通路）来介导替莫唑胺耐药的机理，为胶质瘤耐药理论提供有益补充，为寻找新治疗靶点提供参考依据。

As key vehicles of intercellular communication, exosomes have been implicated in tumorigenesis and recognized as biomarkers of disease and delivery vehicles for clinical application. In our study, we found that miR-151a expression was lower in TMZ-resistant cells and derived exosomes. Upregulation of miR-151a in glioma cells blocked the emergence of acquired TMZ resistance through targeting XRCC4 and ATM. TMZ-resistant cells derived exosomes were delivered to nearby cells, and then disseminated TMZ resistance. Here, we propose a hypothesis that miR-151a may regulate acquisition of TMZ resistance via sequentially modulating Non Homologous End Joining (NHEJ) and Homologous recombination (HR) DNA repair pathway. Now we aim to validate the functional role of miR-151a in targeting of XRCC4-mediated Non Homologous End Joining (NHEJ) and ATM-mediated Homologous Recombination (HR) DNA repair pathway, analyze how intercellular transfer of miR-151a by exosomes disseminates TMZ resistance, and explore the clinical application of circulating and exosomal miR-151a. In summary, our results may provide novel targets and optimize treatment strategies for molecular targeted therapy to overcome TMZ resistance, enhancing the clinical benefits of TMZ therapy in glioma patients.