Gong Dalian, Rao Xinxu, Min Ziqian, Liu Xiaowen, Xin Huan, Zhou Peijun, Yang Lifang, Li Dan
Department of Life Science, College of Biology, Hunan University Changsha 410012, Hunan, China.
Cancer Research Institute, Xiangya School of Medicine, Central South University Changsha 410078, Hunan, China.
Am J Cancer Res. 2023 Aug 15;13(8):3705-3720. eCollection 2023.
Multiple studies have shown that E2 conjugating enzyme family are dysregulated in various cancers and associated with tumor progression and poor prognosis. In present study, we screened and confirmed that UBE2S is one of the E2 conjugating enzymes highly expressed in non-small cell lung cancer (NSCLC), and it plays an oncogenic role by enhancing cell proliferation, migration and stemness in vitro. Using immunoprecipitation technology combined with mass spectrometry assay, we identified ribosomal protein RPL26 as the substrate protein of UBE2S in NSCLC. At the molecular level, overexpression of UBE2S accelerated the ubiquitination and degradation of RPL26, thus upregulating c-Myc to enhance the progression of NSCLC. In addition, the results of a xenograft experiment showed that inhibiting UBE2S could suppress RPL26-c-Myc mediated NSCLC tumor growth in vivo. Our data provided mechanistic evidence supporting the existence of a novel UBE2S-RPL26-c-Myc axis and its critical contribution to progression of NSCLC.
多项研究表明，E2 共轭酶家族在多种癌症中表达失调，并与肿瘤进展和不良预后相关。在本研究中，我们筛选并证实 UBE2S 是在非小细胞肺癌（NSCLC）中高表达的 E2 共轭酶之一，并且它通过在体外增强细胞增殖、迁移和干性发挥致癌作用。利用免疫沉淀技术结合质谱分析，我们鉴定出核糖体蛋白 RPL26 是非小细胞肺癌中 UBE2S 的底物蛋白。在分子水平上，UBE2S 的过表达加速了 RPL26 的泛素化和降解，从而上调 c-Myc 以促进非小细胞肺癌的进展。此外，异种移植实验结果表明，抑制 UBE2S 可在体内抑制 RPL26-c-Myc 介导的非小细胞肺癌肿瘤生长。我们的数据提供了机制证据，支持新型 UBE2S-RPL26-c-Myc 轴的存在及其对非小细胞肺癌进展的关键作用。
