Department of Cell Biology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing 100191, China.
The Affiliated Hospital of Qingdao University, Qingdao 266021, China.
Cell Rep. 2021 Oct 19;37(3):109854. doi: 10.1016/j.celrep.2021.109854.
Despite the tremendous success of targeted and conventional therapies for lung cancer, therapeutic resistance is a common and major clinical challenge. RNF8 is a ubiquitin E3 ligase that plays essential roles in the DNA damage response; however, its role in the pathogenesis of lung cancer is unclear. Here, we report that RNF8 is overexpressed in lung cancer and positively correlates with the expression of p-Akt and poor survival of patients with non-small-cell lung cancer. In addition, we identify RNF8 as the E3 ligase for regulating the activation of Akt by K63-linked ubiquitination under physiological and genotoxic conditions, which leads to lung cancer cell proliferation and resistance to chemotherapy. Together, our study suggests that RNF8 could be a very promising target in precision medicine for lung cancer.
尽管针对肺癌的靶向和常规疗法取得了巨大成功，但治疗耐药性是一个常见且重大的临床挑战。RNF8 是一种泛素 E3 连接酶，在 DNA 损伤反应中发挥重要作用；然而，其在肺癌发病机制中的作用尚不清楚。在这里，我们报告 RNF8 在肺癌中过度表达，并且与 p-Akt 的表达呈正相关，与非小细胞肺癌患者的不良生存相关。此外，我们确定 RNF8 是在生理和遗传毒性条件下通过 K63 连接的泛素化来调节 Akt 激活的 E3 连接酶，从而导致肺癌细胞增殖和对化疗的耐药性。总之，我们的研究表明，RNF8 可能是肺癌精准医学中一个很有前途的靶点。
