RLIM suppresses hepatocellular carcinogenesis by up-regulating p15 and p21

Yongsheng Huang; Meng Nie; Chuang Li; Yingjie Zhao; Jiahui Li; Lan Zhou; Lin Wang

doi:10.18632/oncotarget.20904

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Research Papers:

RLIM suppresses hepatocellular carcinogenesis by up-regulating p15 and p21

Yongsheng Huang, Meng Nie, Chuang Li, Yingjie Zhao, Jiahui Li, Lan Zhou and Lin Wang _

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Oncotarget. 2017; 8:83075-83087. https://doi.org/10.18632/oncotarget.20904

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Abstract

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

Correspondence to:

Lin Wang, email: [email protected]

Keywords: RLIM, hepatocellular carcinogenesis, p15, p21, MIZ1

Received: June 16, 2017 Accepted: August 23, 2017 Published: September 15, 2017

ABSTRACT

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.

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Research Papers:

RLIM suppresses hepatocellular carcinogenesis by up-regulating p15 and p21

Abstract