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Abstract：
Lung cancer is the common malignant tumor with the highest death rate in the world. Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as a potential anticancer agent induces selective apoptotic death of human cancer cells. Unfortunately, approximately half of lung cancer cell lines are intrinsically resistant to TRAIL-induced cell death. In this study, we identified RuvBL1 as a repressor of c-Jun/AP-1 activity, contributing to TRAIL resistance in lung cancer cells. Knocking down RuvBL1 effectively sensitized resistant cells to TRAIL, and overexpression of RuvBL1 inhibited TRAIL-induced apoptosis. Moreover, there was a negative correlation expression between RuvBL1 and c-Jun in lung adenocarcinoma by Oncomine analyses. High expression of RuvBL1 inversely with low c-Jun in lung cancer was associated with a poor overall prognosis. Taken together, our studies broaden the molecular mechanisms of TRAIL resistance and suggest the application of silencing RuvBL1 synergized with TRAIL to be a novel therapeutic strategy in lung cancer treatment.
摘要：
肺癌是世界上逝世亡率最高的常见恶性肿瘤。肿瘤坏死因子相关的凋亡诱导配体（TRAIL）作为潜在的抗癌剂可诱导人类癌细胞的选择性凋亡。不幸的是,大约一半的肺癌细胞系对TRAIL诱导的细胞死亡具有内在抗性。在这项研究中,我们将RuvBL1鉴定为c-Jun/AP-1活性的阻遏物，有助于肺癌细胞中的TRAIL抗性。敲除RuvBL1有效致敏TRAIL抗性细胞，RuvBL1的过表达抑制TRAIL诱导的细胞凋亡。此外，通过Oncomine分析，RuvBL1和c-Jun在肺腺癌中的表达呈负相关。肺癌中RuvBL1的高表达与c-Jun的低表达呈负相关，与整体预后不良相关。一起来看,我们的研究拓宽了TRAIL耐药的分子机制,并提示沉默RuvBL1与TRAIL协同成为肺癌治疗的一种新的治疗策略.
