title: CPEB1 modulates differentiation of glioma stem cells via downregulation of HES1 and SIRT1 expression.
abstract: Glioma stemness has been recognized as the most important reason for glioma relapse and drug resistance. Differentiation of glioma stem cells (GSCs) has been implicated as a novel approach to target recurrent glioma. However, the detailed molecular mechanism involved in the differentiation of GSCs has not yet been elucidated. This study identified CPEB1 as the key modulator that induces the differentiation of GSCs at the post-transcriptional level. Gain and loss of function experiments showed that CPEB1 expression reduced sphere formation ability and the expression of stemness markers such as Nestin and Notch. To elucidate the detailed molecular mechanism underlying the action of CPEB1, we investigated the interacting ribonome of the CPEB1 complex using a Ribonomics approach. CPEB1 specifically suppressed the translation of HES1 and SIRT1 by interacting with a cytoplasmic polyadenylation element. The expression profile of CPEB1 negatively correlated with overall survival in glioma patients. Overexpression of CPEB1 decreased the number of GSCs in an orthotopically implanted glioma animal model. These results suggest that CPEB1-mediated translational control is essential for the differentiation of GSCs and provides novel therapeutic concepts for differentiation therapy.
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. These authors contributed equally to this work.
authors.forename: Jinlong
authors.initials: J
authors.lastname: Yin
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. These authors contributed equally to this work.
authors.forename: Gunwoo
authors.initials: G
authors.lastname: Park
authors.affiliation: Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Jeong Eun
authors.initials: JE
authors.lastname: Lee
authors.affiliation: Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Ju Young
authors.initials: JY
authors.lastname: Park
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Tae-Hoon
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Youn-Jae
authors.initials: YJ
authors.lastname: Kim
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Seung-Hoon
authors.initials: SH
authors.lastname: Lee
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Heon
authors.initials: H
authors.lastname: Yoo
authors.affiliation: Cancer Cell and Molecular Biology Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Jong Heon
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Specific Organs Cancer Branch, Research Institute, National Cancer Center, Goyang, Gyeonggi , Korea. Department of System Cancer Science, Graduate School of Cancer Science and Policy, National Cancer Center, Goyang, Gyeonggi , Korea.
authors.forename: Jong Bae
authors.initials: JB
authors.lastname: Park
mesh_terms: D000818:Animals; D051792:Basic Helix-Loop-Helix Proteins / Q000096:biosynthesis* / Q000235:genetics; D001932:Brain Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D002454:Cell Differentiation / Q000502:physiology; D015536:Down-Regulation; D005260:Female; D005910:Glioma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D057809:HEK293 Cells; D064593:Heterografts; D018398:Homeodomain Proteins / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D014411:Neoplastic Stem Cells / Q000473:pathology*; D056564:Sirtuin 1 / Q000096:biosynthesis* / Q000235:genetics; D000072056:Transcription Factor HES-1; D014157:Transcription Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D014158:Transcription, Genetic; D014162:Transfection; D039221:mRNA Cleavage and Polyadenylation Factors / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D018398:Homeodomain Proteins; D056564:Sirtuin 1; D000072056:Transcription Factor HES-1; D014157:Transcription Factors; D039221:mRNA Cleavage and Polyadenylation Factors; C490386:CPEB1 protein, human; C078493:HES1 protein, human; C447939:SIRT1 protein, human