替莫唑胺(TMZ)耐药是制约胶质瘤患者术后疗效的主要因素，但机制不明。课题组前期： 1）通过LncRNA芯片发现LncRNA SOX2OT在耐TMZ胶质瘤细胞株U87TR中差异高表达，并证实其可能通过SOX2调控TMZ耐药；2）初步证实m6A甲基化修饰关键催化酶在耐TMZ细胞中亦呈差异表达，且与LncRNA SOX2OT表达量有相关性，提示“m6A甲基化极有可能介导了LncRNA SOX2OT调控TMZ耐药”。本研究拟从细胞、动物及临床组织标本三层面：应用定量及免疫印迹技术进行功能学分析，进一步明确m6A修饰参与胶质瘤TMZ耐药；共转染证实m6A修饰系甲基化水平异常介导LncRNA SOX2OT通过SOX2调控耐药；应用RIP、MSP等技术从RNA表观遗传修饰维度探讨m6A修饰介导LncRNA SOX2OT调控TMZ耐药的潜在机制，以期为胶质瘤TMZ耐药机制阐明及临床逆转提供新的理论依据。

Temozolomide(TMZ) resistance is the main factor restricting the postoperative therapeutic effect of patients with glioma, but the mechanism is unknown. In our previous study:1) A novel LncRNA SOX2OT that highly expressed in temozolomide-resistant glioma cells named U87TR was identified through LncRNA microarray, and was initially confirmed that LncRNA SOX2OT may regulate glioma temozolomide resistance through SOX2;2) It was preliminarily confirmed that the expression of the key catalytic enzymes in m6A modification was differentially expressed in TMZ-resistance cells, and was associated with the expression of LncRNA SOX2OT. It is suggested that m6A methylation is highly likely to mediate LncRNA SOX2OT in regulation of TMZ resistance. In this study, we aim to investigate from three aspects including cell, animal and clinical tissue specimens: We use quantitative and immunoblotting technique to analyze the function to further confirm m6A modification involved in glioma TMZ resistance; Using co-transfection assay to confirm m6A modification mediated LncRNA SOX2OT through SOX2 regulates TMZ resistance via abnormal methylation level; Finally, investigate the potential mechanisms of m6A modification mediated LncRNA SOX2OT to regulate TMZ resistance in depth by using RIP\MSP techniques from the RNA epigenetic modification dimension, in order to provide a new theoretical basis for the elucidation and clinical reversal of glioma TMZ resistance mechanism.