腺样囊性癌（adenoid cystic carcinoma,ACC）普遍对化疗耐药。抗氧化应激能力增强是导致肿瘤耐药重要因素。我们前期发现N-myc下调基因（N-myc downregulated gene,NDRG2）在ACC中失活，细胞中过表达NDRG2可提高化疗敏感性，下游抗氧化应激NRF2经典通路抑制；miRNA高通量测序及分析提示NDRG2是ACC中多个上调miRNAs的潜在靶基因，且miRNAs存在ACC驱动基因MYB转录结合位点。我们提出假说：MYB通过上调miRNAs协同失活NDRG2而激活NRF2抗氧化应激经典通路，致ACC化疗不敏感。我们拟利用人体肿瘤、细胞、人源化移植瘤及转基因鼠等，通过质谱、免疫沉淀、荧光素酶等分别从NDRG2上、下游着手研究其介导的氧化应激相关机制。研究首次从ACC驱动基因介导NDRG2调控氧化应激探讨化疗耐药，对提高化疗敏感性具有重要科学意义。

Resistance to chemotherapy is a critical character of adenoid cystic carcinoma (ACC) . The elevating of anti-oxidative stress ability in malignant tumors is an important factor leading to chemo-resistance. Our pre-experiment data showed that tumor-suppressor NDRG2 was inactivated in ACC. Overexpressing NDRG2 in ACC cell lines could significantly increase the chemotherapy sensitivity and the downstream classical NRF2 anti-oxidative pathway was inhibited. High-throughput sequencing and bioinformatics analysis of miRNAs suggested that NDRG2 was a potential target for multiple co-overexpressed oncomiRs (miRNAs act as oncogene) in ACC. Also the promoter regions of these miRNAs have the transcription binding sites of ACC driver gene MYB. We hypothesize that increase of multiple miRNAs modulated by MYB can cooperatively suppress NDRG2 and activate the NRF2 anti-oxidative pathway, resulting in the insensitivity to chemotherapy of ACC. We propose to conduct mass spectrometry, immune coprecipitation, dual luciferase reporter assay, etc. to further explore the cooperative effects of miRNAs upregulated by MYB, the inhibiting on NDRG2 and the downstream mechanisms of mediating oxidative stress through using of human tumor tissues, cells, patient-derived xenografts and transgenic mice. This study is the first to explore the molecular mechanism of chemo-resistance from the perspective of oxidative stress mediated by ACC driver gene, and will provide new ideas for screening the therapeutic target and improving the chemo-sensitivity of ACC.