title: RNA-binding protein PCBP2 modulates glioma growth by regulating FHL3.
abstract: PCBP2 is a member of the poly(C)-binding protein (PCBP) family, which plays an important role in posttranscriptional and translational regulation by interacting with single-stranded poly(C) motifs in target mRNAs. Several PCBP family members have been reported to be involved in human malignancies. Here, we show that PCBP2 is upregulated in human glioma tissues and cell lines. Knockdown of PCBP2 inhibited glioma growth in vitro and in vivo through inhibition of cell-cycle progression and induction of caspase-3-mediated apoptosis. Thirty-five mRNAs were identified as putative PCBP2 targets/interactors using RIP-ChIP protein-RNA interaction arrays in a human glioma cell line, T98G. Four-and-a-half LIM domain 3 (FHL3) mRNA was downregulated in human gliomas and was identified as a PCBP2 target. Knockdown of PCBP2 enhanced the expression of FHL3 by stabilizing its mRNA. Overexpression of FHL3 attenuated cell growth and induced apoptosis. This study establishes a link between PCBP2 and FHL3 proteins and identifies a new pathway for regulating glioma progression.
authors.affiliation: State Key Laboratory of Medical Molecular Biology, Department of Molecular Biology and Biochemistry, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Han
authors.forename: Zhongshuai
authors.initials: Z
authors.lastname: Xin
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Zhao
authors.forename: Wen
authors.initials: W
authors.lastname: Bao
authors.forename: Xihua
authors.initials: X
authors.lastname: Lin
authors.forename: Bin
authors.initials: B
authors.lastname: Yin
authors.forename: Jizong
authors.initials: J
authors.lastname: Zhao
authors.forename: Jiangang
authors.initials: J
authors.lastname: Yuan
authors.forename: Boqin
authors.initials: B
authors.lastname: Qiang
authors.forename: Xiaozhong
authors.initials: X
authors.lastname: Peng
mesh_terms: D000818:Animals; D017209:Apoptosis; D001932:Brain Neoplasms / Q000378:metabolism*; D053148:Caspase 3 / Q000378:metabolism; D002453:Cell Cycle; D045744:Cell Line, Tumor; D047369:Chromatin Immunoprecipitation; D018450:Disease Progression; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005910:Glioma / Q000378:metabolism*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D060588:LIM Domain Proteins / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D016601:RNA-Binding Proteins / Q000378:metabolism*
chemical_list: C117563:FHL3 protein, human; D047908:Intracellular Signaling Peptides and Proteins; D060588:LIM Domain Proteins; C501903:PCBP2 protein, human; D016601:RNA-Binding Proteins; D053148:Caspase 3