UBE2O, an E2/E3 hybrid ubiquitin-protein ligase, has been implicated in the regulation of adipogenesis, erythroid differentiation, and tumor proliferation. However, its role in cancer radioresistance remains completely unknown. Here, we uncover that UBE2O interacts and targets Mxi1 for ubiquitination and degradation at the K46 residue. Furthermore, we show that genetical or pharmacological blockade of UBE2O impairs tumor progression and radioresistance in lung cancer in vitro and in vivo, and these effects can be restored by Mxi1 inhibition. Moreover, we demonstrate that UBE2O is overexpressed and negatively correlated with Mxi1 protein levels in lung cancer tissues. Collectively, our work reveals that UBE2O facilitates tumorigenesis and radioresistance by promoting Mxi1 ubiquitination and degradation, suggesting that UBE2O is an attractive radiosensitization target for the treatment of lung cancer.

UBE2O 是一种 E2/E3 杂化泛素-蛋白质连接酶，与脂肪生成、红细胞分化和肿瘤增殖的调节有关。然而，它在癌症放射抗性中的作用仍然完全未知。在这里，我们发现 UBE2O 相互作用并靶向 Mxi1 以在 K46 残基处进行泛素化和降解。此外，我们表明 UBE2O 的遗传或药理学阻断在体外和体内损害肺癌的肿瘤进展和放射抗性，并且这些影响可以通过 Mxi1 抑制来恢复。此外，我们证明 UBE2O 过表达并与肺癌组织中的 Mxi1 蛋白水平呈负相关。总的来说，我们的工作表明 UBE2O 通过促进 Mxi1 泛素化和降解来促进肿瘤发生和放射抗性，