Shanghai East Hospital, Postgraduate Training Base of Jinzhou Medical University, Shanghai, China.
Research Center for Translational Medicine, Shanghai East Hospital, School of Medicine, Tongji University, Shanghai, China.
Sci Rep. 2024 Oct 10;14(1):23685. doi: 10.1038/s41598-024-74490-6.
Lung cancer is one of the most common types of malignant cancer worldwide, causing a serious social and economic burden. It is classified into non-small cell lung cancer (NSCLC) and small cell lung cancer, with NSCLC accounting for 80-85% of cases. Eukaryotic translation initiation factor 4 gamma 1 (EIF4G1) is highly expressed in NSCLC, playing an important role in regulating tumor growth, angiogenesis, malignant transformation, and phagocytosis. Ubiquitin-specific protease 10 (USP10) functions as a deubiquitinating enzyme to regulate substrate protein deubiquitination and reverse the ubiquitin proteasome degradation pathway. Our previous study identified an interaction between EIF4G1 and USP10; however, their regulatory mechanism remains unclear. Herein, we found that USP10 positively regulates EIF4G1 in NSCLC cells. An in vivo ubiquitination assay demonstrated deubiquitination of EIF4G1 by USP10, which reversed the ubiquitin proteasomal degradation of EIF4G1, thereby increasing its stability. Upregulation of EIF4G1 promoted cell proliferation, migration, and invasion in NSCLC cells. The current study not only reveals a novel mechanism through which USP10 positively regulates EIF4G1 in NSCLC, but also demonstrates the potential of USP10 as a therapeutic target to treat NSCLC.
肺癌是全球最常见的恶性肿瘤之一，给社会和经济带来了严重的负担。它分为非小细胞肺癌（NSCLC）和小细胞肺癌，其中 NSCLC 占 80-85%。真核翻译起始因子 4 伽马 1（EIF4G1）在 NSCLC 中高度表达，在调节肿瘤生长、血管生成、恶性转化和吞噬作用方面发挥着重要作用。泛素特异性蛋白酶 10（USP10）作为一种去泛素化酶，调节底物蛋白去泛素化并逆转泛素蛋白酶体降解途径。我们之前的研究确定了 EIF4G1 和 USP10 之间的相互作用；然而，它们的调节机制尚不清楚。在此，我们发现 USP10 在 NSCLC 细胞中正向调节 EIF4G1。体内泛素化试验表明 USP10 对 EIF4G1 进行去泛素化，从而逆转了 EIF4G1 的泛素蛋白酶体降解，增加了其稳定性。EIF4G1 的上调促进了 NSCLC 细胞的增殖、迁移和侵袭。本研究不仅揭示了 USP10 正向调节 NSCLC 中 EIF4G1 的新机制，还表明 USP10 可能成为治疗 NSCLC 的治疗靶点。
