title: Cellular nucleic acid binding protein suppresses tumor cell metastasis and induces tumor cell death by downregulating heterogeneous ribonucleoprotein K in fibrosarcoma cells.
abstract: BACKGROUND
  Cellular nucleic acid binding protein (CNBP) has been implicated in vertebrate craniofacial development and in myotonic dystrophy type 2 (DM2) and sporadic inclusion body myositis (sIBM) human diseases by controlling cell proliferation and survival to mediate neural crest expansion. CNBP has been found to bind single-stranded nucleic acid and promote rearrangements of nucleic acid secondary structure in an ATP-independent manner, acting as a nucleic acid chaperone.
  
  
  METHODS
  A variety of methods were used, including cell viability assays, wound-scratch assays, chemotaxis assays, invasion assays, circular dichroic (CD) spectroscopy, NMR spectroscopy, chromatin immunoprecipitation, expression and purification of recombinant human CNBP, electrophoretic mobility shift assay (EMSA), surface plasmon resonance (SPR), fluorescence resonance energy transfer (FRET) analyses, luciferase reporter assay, Western blotting, and isothermal titration calorimetry (ITC).
  
  
  RESULTS
  Up-regulation of CNBP induced human fibrosarcoma cell death and suppressed fibrosarcoma cell motility and invasiveness. It was found that CNBP transcriptionally down-regulated the expression of heterogeneous ribonucleoprotein K (hnRNP K) through its conversion of a G-rich sequence into G-quadruplex in the promoter of hnRNP K. G-quadruplex stabilizing ligand tetra-(N-methyl-4-pyridyl) porphyrin (TMPyP4) could interact with and stabilize the G-quadruplex, resulting in downregulation of hnRNP K transcription.
  
  
  CONCLUSIONS
  CNBP overexpression caused increase of cell death and suppression of cell metastasis through its induction of G-quadruplex formation in the promoter of hnRNP K resulting in hnRNP K down-regulation.
  
  
  CONCLUSIONS
  The present result provided a new solution for controlling hnRNP K expression, which should shed light on new anticancer drug design and development.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Qiu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Siqi
authors.initials: S
authors.lastname: Chen
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Lijuan
authors.initials: L
authors.lastname: Su
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Jinggong
authors.initials: J
authors.lastname: Liu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Nannan
authors.initials: N
authors.lastname: Xiao
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Tian-Miao
authors.initials: TM
authors.lastname: Ou
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China.
authors.forename: Jia-Heng
authors.initials: JH
authors.lastname: Tan
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China. Electronic address: cesglq@mail.sysu.edu.cn.
authors.forename: Lian-Quan
authors.initials: LQ
authors.lastname: Gu
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China. Electronic address: ceshzs@mail.sysu.edu.cn.
authors.forename: Zhi-Shu
authors.initials: ZS
authors.lastname: Huang
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou University City, 132 Waihuan East Road, Guangzhou 510006, PR China. Electronic address: liding@mail.sysu.edu.cn.
authors.forename: Ding
authors.initials: D
authors.lastname: Li
mesh_terms: D016923:Cell Death / Q000235:genetics; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000235:genetics; D047369:Chromatin Immunoprecipitation; D005354:Fibrosarcoma / Q000235:genetics* / Q000473:pathology; D031541:Fluorescence Resonance Energy Transfer; D054856:G-Quadruplexes; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D034641:Heterogeneous-Nuclear Ribonucleoprotein K / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D009362:Neoplasm Metastasis; D009696:Nucleic Acids / Q000235:genetics; D011401:Promoter Regions, Genetic; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C433227:CNBP protein, human; D034641:Heterogeneous-Nuclear Ribonucleoprotein K; D009696:Nucleic Acids; D016601:RNA-Binding Proteins
keywords: CNBP; Cell death; G-quadruplex; Metastasis; Transcriptional regulation; hnRNP K