Small ubiquitin-related modifier 1 is involved in hepatocellular carcinoma progression via mediating p65 nuclear translocation
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Jun Liu1,2,3, Xiaofang Tao1,3, Jin Zhang2,3, Peng Wang1,3, Manqi Sha2,3, Yong Ma4, Xiaoping Geng5, Lijie Feng1,3, Yujun Shen1,3, Yifan Yu6, Siying Wang1, Shengyun Fang1,3,7, Yuxian Shen1,2,3
1School of Basic Medical Sciences, Anhui Medical University, Hefei, China
2School of Pharmacy, Anhui Medical University, Hefei, China
3Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China
4Chinese People's Liberation Army 123 Hospital, Bengbu, China
5The First Affiliated Hospital, Anhui Medical University, Hefei, China
6Actuarial Science, School of Continuing Education, Columbia University, New York, NY, USA
7Center for Biomedical Engineering and Technology, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA
Yuxian Shen, e-mail: [email protected]
Keywords: SUMO1, SUMOylation, hepatocellular carcinoma, p65, NF-κB
Received: October 05, 2015 Accepted: February 23, 2016 Published: March 14, 2016
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.
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