title: CPEB1, a histone-modified hypomethylated gene, is regulated by miR-101 and involved in cell senescence in glioma.
abstract: Epigenetic mechanisms have important roles in carcinogenesis. We certified that the mRNA translation-related gene cytoplasmic 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 methyltransferase enhancer of zeste homolog 2 (EZH2) and embryonic ectoderm development (EED) are direct targets of miR-101. We demonstrated that miR-101 downregulated the expression of CPEB1 through reversing the methylation status of the CPEB1 promoter by regulating the presence on the promoter of the methylation-related histones H3K4me2, H3K27me3, H3K9me3 and H4K20me3. The epigenetic regulation of H3K27me3 on CPEB1 promoter is mediated by EZH2 and EED. EZH2 has a role in the regulation of H3K4me2. Furthermore, the downregulation of CPEB1 induced senescence in a p53-dependent manner.
authors.affiliation: Cancer Research Institute, Central South University, Changsha, China.
authors.forename: L
authors.initials: L
authors.lastname: Xiaoping
authors.forename: Y
authors.initials: Y
authors.lastname: Zhibin
authors.forename: L
authors.initials: L
authors.lastname: Wenjuan
authors.forename: W
authors.initials: W
authors.lastname: Zeyou
authors.forename: X
authors.initials: X
authors.lastname: Gang
authors.forename: L
authors.initials: L
authors.lastname: Zhaohui
authors.forename: Z
authors.initials: Z
authors.lastname: Ying
authors.forename: W
authors.initials: W
authors.lastname: Minghua
authors.forename: L
authors.initials: L
authors.lastname: Guiyuan
mesh_terms: D020413:3' Untranslated Regions; D000328:Adult; D001483:Base Sequence; D001665:Binding Sites; D001932:Brain Neoplasms / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D016922:Cellular Senescence; D019175:DNA Methylation; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D016147:Genes, Tumor Suppressor; D005910:Glioma / Q000235:genetics* / Q000401:mortality / Q000473:pathology; D006657:Histones / Q000378:metabolism; D006801:Humans; D008297:Male; D035683:MicroRNAs / Q000235:genetics*; D011379:Prognosis; D011401:Promoter Regions, Genetic; D021381:Protein Transport; D034622:RNA Interference; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D039221:mRNA Cleavage and Polyadenylation Factors / Q000235:genetics* / Q000378:metabolism
chemical_list: D020413:3' Untranslated Regions; C490386:CPEB1 protein, human; D006657:Histones; C534072:MIRN101 microRNA, human; D035683:MicroRNAs; C495901:TP53 protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; D039221:mRNA Cleavage and Polyadenylation Factors