RLIM suppresses hepatocellular carcinogenesis by up-regulating p15 and p21
Autor: | Lan Zhou, Lin Wang, Yingjie Zhao, Chuang Li, Meng Nie, Jiahui Li, Yongsheng Huang |
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Jazyk: | angličtina |
Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
MIZ1 medicine.disease_cause p15 law.invention 03 medical and health sciences Transcription (biology) law Medicine RLIM biology hepatocellular carcinogenesis p21 business.industry Cell growth Kinase medicine.disease Ubiquitin ligase 030104 developmental biology Oncology Apoptosis Hepatocellular carcinoma Immunology biology.protein Cancer research Suppressor business Carcinogenesis Research Paper |
Zdroj: | Oncotarget |
ISSN: | 1949-2553 |
Popis: | // Yongsheng Huang 1, * , Meng Nie 1, * , Chuang Li 1 , Yingjie Zhao 2 , Jiahui Li 1 , Lan Zhou 1 and Lin Wang 1 1 Department of Physiology, Peking Union Medical College, Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences, Beijing 100005, China 2 Department 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: lin.wang@ibms.pumc.edu.cn 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. |
Databáze: | OpenAIRE |
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