去泛素化酶JOSD2促进肝癌细胞的存活和转移

蛋白质泛素化是一种可逆的蛋白质翻译后修饰,在信号转导和蛋白质稳定性调控中发挥关键作用。去泛素化酶调控在许多种肿瘤中的作用机制尚不清楚。本文对63种去泛素化酶在肝细胞癌病人的生存和预后进行分析,发现去泛素化酶JOSD2(josephin domain containing 2)在肝细胞癌组织中表达显著高于癌旁(P<0.0001),且与总生存期相关(P<0.05)。JOSD2属于去泛素化酶MJD(machado josephin domain)亚家族成员,该家族其它成员与肝细胞癌发生无显著的相关性。对TCGA(The Cancer Genome Atlas)数据中JOSD2高表达样本和低表达样本的差异基因进行功能富集分析,显示JOSD2高表达样本中与细胞增殖相关通路显著富集(FDR<0.05)。在肝癌细胞系中过表达JOSD2,发现其能促进肝癌细胞的存活、迁移和侵袭(P<0.01)。综上所述,本文发现去泛素化酶JOSD2在肝细胞癌组织中高表达,高表达JOSD2的肝细胞癌病人总生存期显著降低(P=0.041),过表达JOSD2能促进肝癌细胞的存活和转移,提示JOSD2可能促进肝细胞癌的转移。

Deubiquitinase JOSD2 Promotes the Survival and Metastasis of Hepatoma Cells

Ubiquitination is a reversible post-translational modification that regulates protein stability and plays a function in numerous signaling pathways. Deubiquitinases play important roles in the regulation of the occurrence and development of different cancers. In this study, we analyzed the survival and prognosis of liver cancer patients according to the expression levels of 63 deubiquitinases. Results discovered that JOSD2 expression in tumor was significantly higher than that in the adjacent tissue (P<0.0001) and was negatively associated with overall survival of patients (P<0.05). JOSD2 is a deubiquitinase from MJD sub-family. Other members of this sub-family were not correlated with liver cancer. The pathways related to cell proliferation were significantly enriched (FDR<0.05) in a differential gene function enrichment analysis of JOSD2 high-expressing samples in TCGA data. In hepatoma cell lines, we demonstrated that the overexpression of JOSD2 significantly enhances cell survival, migration and invasion. In conclusion, this study found that JOSD2 is highly expressed in liver cancer (P=0.041), and that patients with high-expressed JOSD2 have significantly shorter overall survival. Furthermore, overexpression of JOSD2 can promote the survival and metastasis of hepatoma cells (P<0.01), which suggests that JOSD2 might promote the survival and metastasis of hepatocellular carcinoma.