CPEB1,a histone-modified hypomethylated gene,is regulated by miR-101 and involved in cell senescence

• 作 者: Xiaoping Liu Zhibin Yu Wenjuan Li Zeyou Wang Gang Xu Zhaohui Luo Ying Zheng Minghua Wu Guiyuan Li
• 机 构: Cancer Research Institute,Central South University,Changsha,Hunan,China;Key Laboratory of Carcinogen
• 出 处: 中国病理生理学会第十四届肿瘤专业委员会、第十五届免疫专业委员会联合学术会议
• 发表日期: 2014年4期
• 关键词: hypomethylation histone-modifition miR-101 CPEB 1 p53 senescence

　　Epigenetic mechanisms play important roles in carcinogenesis.We certifiedthat the mRNA translation-related genecytoplasmic polyadenylation element-binding protein 1 (CPEB1) is hypomethylated and overexpressed in glioma cells and tissues.The knockdown of CPEB1 reduced cell senescence by regulating the expression or distribution of p53 in glioma cells.CPEB1 is also regulated directly by the tumor suppressor miR-101,a potential marker of glioma.It is known that the histone methyltransferasesenhancer of zeste homolog 2 (EZH2) andembryonic ectoderm development (EED) are direct targets of miR-101.And we demonstrated that miR-101 downregulated the expression of CPEB1 through reversing the methylation status of the CPEB1 promoter by regulating the presenceon the promoter of the methylation-related histones H3K4me2,H3K27me3,H3K9me3 and H4K20me3.The epigenetically regulation of H3K27me3 on CPEB1 promoter is partially mediated by EZH2 and EED.EZH2 and plays a role in the regulation of H3K4me2.Furthermore,the downregulation of CPEB1 induced senescence in a p53-dependent manner.