Radiation resistance affects survival in non-small-cell lung cancer (NSCLC) patients. Further exploration of mechanisms and targets is urgently needed. Using bioinformatic analyses, we found that UBE2T is associated with survival, tumor size, lymph node metastasis and distant metastasis. Then, real-time PCR and immunohistochemistry were performed to explore the differentially expressed genes between normal and NSCLC tissues. Furthermore, we used colony formation, EdU incorporation, scratch, transwell assays, flow cytometry, immunofluorescence and western blot to assess the role of UBE2T in vitro and in vivo. RNA-Seq and coimmunoprecipitation were used to explore the mechanism. The results showed that UBE2T promotes proliferation, migration, invasion, and radiation resistance in vitro and in vivo by accelerating the G2/M transition and inhibiting apoptosis. Mechanistically, UBE2T promotes epithelial-mesenchymal transition (EMT) via ubiquitination-mediated FOXO1 degradation and Wnt/β-catenin signaling pathway activation. Moreover, FOXO1 reversed radiation resistance and EMT. Therefore, UBE2T may be a potential target for enhancing radiotherapy sensitivity and serve as a biomarker to predict prognosis.

辐射抗性影响非小细胞肺癌 (NSCLC) 患者的生存。迫切需要进一步探索机制和目标。使用生物信息学分析，我们发现 UBE2T 与生存率、肿瘤大小、淋巴结转移和远处转移有关。然后，进行实时PCR和免疫组织化学以探索正常和NSCLC组织之间的差异表达基因。此外，我们使用集落形成、EdU 掺入、划痕、transwell 检测、流式细胞术、免疫荧光和蛋白质印迹来评估 UBE2T 在体外和体内的作用。RNA-Seq 和免疫共沉淀用于探索机制。结果表明，UBE2T 促进增殖、迁移、侵袭、通过加速 G2/M 转变和抑制细胞凋亡，在体外和体内抗辐射。从机制上讲，UBE2T 通过泛素化介导的 FOXO1 降解和 Wnt/β-catenin 信号通路激活促进上皮间质转化 (EMT)。此外，FOXO1 逆转了辐射阻力和 EMT。因此，UBE2T 可能成为提高放射治疗敏感性的潜在靶点，并作为预测预后的生物标志物。