title: The histone deacetylase SIRT6 suppresses the expression of the RNA-binding protein PCBP2 in glioma.
abstract: More than 80% of tumors that occur in the brain are malignant gliomas. The prognosis of glioma patients is still poor, which makes glioma an urgent subject of cancer research. Previous evidence and our present data show that PCBP2 is over-expressed in human glioma tissues and predicts poor outcome. However, the mechanism by which PCBP2 is regulated in glioma remains elusive. We find that SIRT6, one of the NAD(+)-dependent class III deacetylase SIRTUINs, is down-regulated in human glioma tissues and that the level of SIRT6 is negatively correlated with PCBP2 level while H3K9ac enrichment on the promoter of PCBP2 is positively correlated with PCBP2 expression. Furthermore, we identify PCBP2 as a target of SIRT6. We demonstrate that PCBP2 expression is inhibited by SIRT6, which depends upon deacetylating H3K9ac. Finally, our results reveal that SIRT6 inhibits glioma cell proliferation and colony formation in vitro and glioma cell growth in vivo in a PCBP2 dependent manner. In summary, our findings implicate that SIRT6 inhibits PCBP2 expression through deacetylating H3K9ac and SIRT6 acts as a tumor suppressor in human glioma.
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Chen
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Hao
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Dongwei
authors.initials: D
authors.lastname: Dai
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Guosheng
authors.initials: G
authors.lastname: Han
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Zhijian
authors.initials: Z
authors.lastname: Yue
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China.
authors.forename: Laixing
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: yiquancao@sohu.com.
authors.forename: Yiqun
authors.initials: Y
authors.lastname: Cao
authors.affiliation: Department of Neurosurgery, Changhai Hospital, Second Military Medical University, Shanghai 200433, China. Electronic address: jianminliuchh@163.com.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Liu
mesh_terms: D000107:Acetylation; D000818:Animals; D001932:Brain Neoplasms / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D005910:Glioma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D064593:Heterografts; D006657:Histones / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D051379:Mice; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000037:antagonists & inhibitors / Q000235:genetics*; D037761:Sirtuins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D025521:Tumor Suppressor Proteins / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D006657:Histones; C501903:PCBP2 protein, human; D016601:RNA-Binding Proteins; D025521:Tumor Suppressor Proteins; C516592:SIRT6 protein, human; D037761:Sirtuins
keywords: Glioma; H3K9ac; PCBP2; SIRT6