Huang Yongsheng, Nie Meng, Li Chuang, Zhao Yingjie, Li Jiahui, Zhou Lan, Wang Lin
Department of Physiology, Peking Union Medical College, Chinese Academy of Medical Sciences, Institute of Basic Medical Sciences, Beijing 100005, China.
Department of Genetics, Albert Einstein College of Medicine, Bronx, NY 10461, U.S.A.
Oncotarget. 2017 Sep 15;8(47):83075-83087. doi: 10.18632/oncotarget.20904. eCollection 2017 Oct 10.
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.
肝细胞癌的发生是由于影响细胞增殖、分化和凋亡的癌基因和肿瘤抑制基因失调所致。p15和p21是细胞周期蛋白依赖性激酶抑制剂，可阻止细胞增殖并作为关键的肿瘤抑制因子。在此我们报告，E3泛素连接酶RLIM在肝细胞癌患者中的表达下调，并且在临床进展中与p15和p21的表达相关。此外，我们表明RLIM的过表达抑制肝细胞癌的细胞生长并阻止细胞周期进程。从机制上讲，我们发现RLIM直接与MIZ1结合，破坏c-MYC与MIZ1之间的相互作用，并增强p15和p21的转录。我们的结果表明，RLIM是肝细胞癌发生过程中的重要抑制因子。
