title: Small ubiquitin-related modifier 1 is involved in hepatocellular carcinoma progression via mediating p65 nuclear translocation.
abstract: 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.
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.|School of Pharmacy, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Xiaofang
authors.initials: X
authors.lastname: Tao
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Jin
authors.initials: J
authors.lastname: Zhang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Peng
authors.initials: P
authors.lastname: Wang
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Manqi
authors.initials: M
authors.lastname: Sha
authors.affiliation: Chinese People's Liberation Army 123 Hospital, Bengbu, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: Ma
authors.affiliation: The First Affiliated Hospital, Anhui Medical University, Hefei, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Geng
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Lijie
authors.initials: L
authors.lastname: Feng
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Yujun
authors.initials: Y
authors.lastname: Shen
authors.affiliation: Actuarial Science, School of Continuing Education, Columbia University, New York, NY, USA.
authors.forename: Yifan
authors.initials: Y
authors.lastname: Yu
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.
authors.forename: Siying
authors.initials: S
authors.lastname: Wang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.|Center for Biomedical Engineering and Technology, Department of Physiology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: Shengyun
authors.initials: S
authors.lastname: Fang
authors.affiliation: School of Basic Medical Sciences, Anhui Medical University, Hefei, China.|School of Pharmacy, Anhui Medical University, Hefei, China.|Biopharmaceutical Research Institute, Anhui Medical University, Hefei, China.
authors.forename: Yuxian
authors.initials: Y
authors.lastname: Shen
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000502:physiology; D006528:Carcinoma, Hepatocellular / Q000378:metabolism / Q000473:pathology*; D018450:Disease Progression; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism / Q000473:pathology*; D025842:SUMO-1 Protein / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*
chemical_list: D025842:SUMO-1 Protein; C495501:SUMO1 protein, human; D051996:Transcription Factor RelA
keywords: NF-κB; SUMO1; SUMOylation; hepatocellular carcinoma; p65