Small ubiquitin-related modifier 1 is involved in hepatocellular carcinoma progression via mediating p65 nuclear translocation.
Small ubiquitin-related modifier 1 is involved in hepatocellular carcinoma progression via mediating p65 nuclear translocation.
复制标题
小泛素相关修饰剂 1 通过介导 p65 核易位参与肝细胞癌进展
DOI：
10.18632/oncotarget.8066
复制
发表时间：
2016-04-19
期刊：
影响因子：
--
通讯作者：
Shen Y
中科院分区：
文献类型：
--
作者：
Liu J;Tao X;Zhang J;Wang P;Sha M;Ma Y;Geng X;Feng L;Shen Y;Yu Y;Wang S;Fang S;Shen Y
小泛素相关修饰蛋白（SUMO）参与翻译后修饰，称为SUMO化，并调节各种细胞内过程，如靶向蛋白质的核输入。p65的核转运导致NF-κB的活化，并且p65含有多个SUMO相互作用基序（西姆斯）。然而，p65和SUMO 1在肝细胞癌（HCC）中的关系仍不清楚。在这项研究中，我们证明了SUMO 1通过调节p65亚细胞定位在HCC中的潜在作用。我们发现，无论是SUMO 1-或p65-阳性免疫反应显着增加，在肝癌患者的肿瘤组织细胞核与非肿瘤组织相比，进一步分析表明，SUMO 1-和核p65-阳性免疫反应之间的相关性（R = 0.851，P = 0.002）。我们还通过免疫共沉淀验证了p65和SUMO 1在HCC中的相互作用。TNF-α和缺氧增加SUMO 1蛋白水平，并增强SUMO 1修饰的p65 SUMO化。此外，SUMO 1基因的敲低还可降低p65核转位，抑制NF-κB的转录活性。进一步的研究结果表明，SUMO 1的敲低抑制了肝癌细胞的增殖和迁移。这些结果表明SUMO 1通过促进p65核转位和调节NF-κB活性参与HCC的进展。
Small ubiquitin-related modifier (SUMO) proteins participate in a post-translational modification called SUMOylation and regulate a variety of intracellular processes, such as targeting proteins for nuclear import. The nuclear transport of p65 results in the activation of NF-κB, and p65 contains several SUMO interacting motifs (SIMs). However, the relationship between p65 and SUMO1 in hepatocellular carcinoma (HCC) remains unclear. In this study, we demonstrated the potential roles of SUMO1 in HCC via the regulation of p65 subcellular localization. We found that either SUMO1- or p65-positive immunoreactivity was remarkably increased in the nuclei of tumor tissues in HCC patients compared with non-tumor tissues, and further analysis suggested a correlation between SUMO1- and nuclear p65-positive immunoreactivities (R = 0.851, P = 0.002). We also verified the interaction between p65 and SUMO1 in HCC by co-immunoprecipitation. TNF-α and hypoxia increased SUMO1 protein levels and enhanced SUMO1-modified p65 SUMOylation. Moreover, the knockdown of SUMO1 decreased p65 nuclear translocation and inhibited NF-κB transcriptional activity. Further the results of this study revealed that the knockdown of SUMO1 suppressed the proliferation and migration of hepatoma cells. These results suggest that SUMO1 contributes to HCC progression by promoting p65 nuclear translocation and regulating NF-κB activity.
登录
查看更多内容
影响因子：
4
作者：
Chen, Shuliang;Yu, Xiao;Guo, Deyin
通讯作者：
Guo, Deyin
影响因子：
5.3
作者：
Dahan, Jennifer;Nouet, Yann;Wei, Yu
通讯作者：
Wei, Yu
影响因子：
4.8
作者：
Ferreira, V;Tarantino, N;Körner, M
通讯作者：
Körner, M
影响因子：
4.3
作者：
Baek, Sung Hee
通讯作者：
Baek, Sung Hee
影响因子：
3.6
作者：
Kim, Eun Mi;Lee, Han-Hyoung;Chun, Taehoon
通讯作者：
Chun, Taehoon