RLIM suppresses hepatocellular carcinogenesis by up-regulating p15 and p21
Metrics: PDF 1015 views | HTML 1854 views | ?
Yongsheng Huang1,*, Meng Nie1,*, Chuang Li1, Yingjie Zhao2, Jiahui Li1, Lan Zhou1 and Lin Wang1
1Department of Physiology, Peking Union Medical College, Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences, Beijing 100005, China
2Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, U.S.A
*These authors have contributed equally to this work
Lin Wang, email: [email protected]
Keywords: RLIM, hepatocellular carcinogenesis, p15, p21, MIZ1
Received: June 16, 2017 Accepted: August 23, 2017 Published: September 15, 2017
Hepatocellular carcinogenesis results from dysregulation of oncogenes and tumor suppressors that influence cellular proliferation, differentiation and apoptosis. p15 and p21 are cyclin-dependent kinase inhibitors, which arrest cell proliferation and serve as critical tumor suppressors. Here we report that the E3 ubiquitin ligase RLIM expression is downregulated in hepatocellular carcinoma patients, and correlated with p15 and p21 expression in clinical progression. In addition, we showed that RLIM overexpression suppresses the cell growth and arrests cell cycle progression of hepatocellular carcinoma. Mechanistically, we found that RLIM directly binds to MIZ1, disrupting the interaction between c-MYC and MIZ1, and enhancing p15 and p21 transcription. Our results demonstrate that RLIM is an important suppressor in hepatocellular carcinogenesis.
All site content, except where otherwise noted, is licensed under a Creative Commons Attribution 3.0 License.