Ma Xingjie, Zhao Junjie, Yang Fan, Liu Haitao, Qi Weibo
Department of Cardiothoracic Surgery, The First Affiliated Hospital of Jiaxing University, Jiaxing, Zhejiang, China.
Oncotarget. 2017 Aug 24;8(48):84193-84203. doi: 10.18632/oncotarget.20449. eCollection 2017 Oct 13.
The molecular pathogenesis of human lung cancer has not been completely clarified. Here, we reported that UBE2L3, a member of the ubiquitin-conjugating enzymes (E2s), were overexpressed in non-small-cell lung cancer (NSCLC) tissues compared with the non-tumor tissues. High expression of UBE2L3 was correlated with advanced tumor stage and adverse outcomes. Knockdown of UBE2L3 inhibited NSCLC cell growth while ectopic expression of UBE2L3 promoted NSCLC cell growth in a cell cycle dependent manner. The results of subcutaneous tumor xenograft studies revealed that knockdown of UBE2L3 attenuated the tumor growth. Mechanistically, we observed that UBE2L3 could interact with F-box protein Skp2, a member of the SCF (Skp2) ubiquitin ligase complex, and thus promoted the ubiquitination and proteasomal degradation of p27kip1. Furthermore, NSCLC cases with high level of UBE2L3 and low level of p27kip1 had worst prognosis, suggesting that combination of UBE2L3 and p27kip1 is a more powerful prognostic marker for NSCLC patients. Taken together, the current study presented a novel marker for predicting prognosis and a potential therapeutic target for NSCLC patients.
人类肺癌的分子发病机制尚未完全阐明。在此，我们报告称，泛素结合酶（E2s）成员之一的UBE2L3在非小细胞肺癌（NSCLC）组织中相较于非肿瘤组织呈过表达。UBE2L3的高表达与肿瘤晚期及不良预后相关。敲低UBE2L3可抑制NSCLC细胞生长，而异位表达UBE2L3则以细胞周期依赖的方式促进NSCLC细胞生长。皮下肿瘤异种移植研究结果显示，敲低UBE2L3可减弱肿瘤生长。机制上，我们观察到UBE2L3可与F-box蛋白Skp2（SCF（Skp2）泛素连接酶复合体的成员）相互作用，从而促进p27kip1的泛素化和蛋白酶体降解。此外，UBE2L3水平高且p27kip1水平低的NSCLC病例预后最差，这表明UBE2L3和p27kip1的联合是NSCLC患者更有力的预后标志物。综上所述，本研究提出了一种预测NSCLC患者预后的新标志物及潜在治疗靶点。
