Ma Xingjie, Qi Weibo, Yang Fan, Pan Huan
Department of Cardiothoracic Surgery, First Affiliated Hospital of Jiaxing University Jiaxing 314001, Zhejiang, China.
Department of Central Laboratory, First Affiliated Hospital of Jiaxing University Jiaxing 314001, Zhejiang, China.
Am J Cancer Res. 2022 May 15;12(5):2323-2336. eCollection 2022.
Accumulating evidence suggests that the deubiquitinase JOSD1 accounts for aggressiveness and unfavorable prognosis in multiple human cancers. But, the significance of JOSD1 in lung adenocarcinoma (LUAD) is elusive. We established that JOSD1 was aberrantly overexpressed in LUAD tissues, relative to normal tissues. Elevated JOSD1 levels in LUAD tissues positively related to advanced clinicopathological characteristics and poor overall survival (OS) in LUAD patients. Furthermore, we found that JOSD1 knockdown suppressed tumor cell proliferation and metastasis, whereas overexpression of JOSD1 led to opposite phenotypes. Mechanistically, JOSD1 stabilized Snail protein through deubiquitination, which promotes the epithelial-to-mesenchymal transition (EMT) process. Indeed, JOSD1 promoted tumor cell invasion as well as metastasis on the dependence of Snail. The protein expression analysis of LUAD tissues indicated that JOSD1 positively correlated with Snail. Moreover, JOSD1 and Snail co-overexpression had the worst prognosis in LUAD patients. Overall, these results demonstrated that JOSD1 was significantly overexpressed in LUAD and stabilized Snail via deubiquitination to promote LUAD metastasis.
越来越多的证据表明，去泛素化酶JOSD1在多种人类癌症中导致侵袭性和不良预后。但是，JOSD1在肺腺癌（LUAD）中的意义尚不清楚。我们发现，相对于正常组织，JOSD1在LUAD组织中异常过表达。LUAD组织中JOSD1水平升高与LUAD患者的晚期临床病理特征和较差的总生存期（OS）呈正相关。此外，我们发现敲低JOSD1可抑制肿瘤细胞增殖和转移，而JOSD1过表达则导致相反的表型。从机制上讲，JOSD1通过去泛素化使Snail蛋白稳定，从而促进上皮-间质转化（EMT）过程。实际上，JOSD1在依赖Snail的情况下促进肿瘤细胞侵袭和转移。LUAD组织的蛋白质表达分析表明，JOSD1与Snail呈正相关。此外，JOSD1和Snail共同过表达的LUAD患者预后最差。总体而言，这些结果表明，JOSD1在LUAD中显著过表达，并通过去泛素化使Snail稳定，从而促进LUAD转移。
