title: Integrative genomic and proteomic analyses identifies glycerol-3-phosphate acyltransferase as a target of low-dose ionizing radiation in EBV infected-B cells.
abstract: OBJECTIVE
  We sought to gain a better understanding of the low-dose ionizing radiation (LDIR)-induced molecular changes in transformed pre-malignant cells in their microenvironment.
  
  
  METHODS
  The cellular response to LDIR was compared and contrasted using immortalized human Epstein-Barr virus-infected B-cells (EBV-B) in mono-culture, co-culture with human bone marrow derived stromal cells (MSC), or under the LDIR-induced bystander effect. The resulting alterations in protein and gene expression (including microRNA, miRNA) were evaluated by isobaric tags for relative and absolute quantification (iTRAQ) proteomics assay, western blot, cDNA array and quantitative reverse transcription polymerase chain reaction (RT-PCR), respectively.
  
  
  RESULTS
  The miRNAs let7a, miR-15b, miR-16, and miR-21, and a lipid metabolic miRNA hub miR-23b, were upregulated after LDIR exposure in the mono-cultured EBV-B cells, but were downregulated in EBV-B cells co-irradiated with MSC. A lipid biosynthesis enzyme glycerol-3-phosphate acyltransferase, the common target of these miRNA, was downregulated at the level of protein and mRNA expression in the LDIR-exposed, mono-cultured EBV-B cells and upregulated MSC co-cultured EBV-B cells.
  
  
  CONCLUSIONS
  These results suggest a putative miRNA regulatory mechanism controlling the LDIR-induced stress response, and illustrate that LDIR exposure, and the cell's microenvironment, can affect specific gene expression, both directly and indirectly, resulting in altered protein expression.
authors.affiliation: a Department of Laboratory Medicine , Juntendo University , Tokyo ;|i Department of Leukemia , the University of Texas MD Anderson Cancer Center , Houston , Texas , USA ;
authors.forename: Yoko
authors.initials: Y
authors.lastname: Tabe
authors.affiliation: a Department of Laboratory Medicine , Juntendo University , Tokyo ;
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Hatanaka
authors.affiliation: b Department of Radiology , Juntendo University , Tokyo ;
authors.forename: Mayumi
authors.initials: M
authors.lastname: Nakashiro
authors.affiliation: a Department of Laboratory Medicine , Juntendo University , Tokyo ;|k Leading Center for the Development and Research of Cancer Medicine , Juntendo University , Tokyo , Japan.
authors.forename: Kazumasa
authors.initials: K
authors.lastname: Sekihara
authors.affiliation: a Department of Laboratory Medicine , Juntendo University , Tokyo ;|k Leading Center for the Development and Research of Cancer Medicine , Juntendo University , Tokyo , Japan.
authors.forename: Shinichi
authors.initials: S
authors.lastname: Yamamoto
authors.affiliation: c Department of Laboratory Medicine , Tokai University School of Medicine , Kanagawa ;
authors.forename: Hiromichi
authors.initials: H
authors.lastname: Matsushita
authors.affiliation: d BioMedical Research Center, Juntendo University , Tokyo ;
authors.forename: Saiko
authors.initials: S
authors.lastname: Kazuno
authors.affiliation: d BioMedical Research Center, Juntendo University , Tokyo ;|e Laboratory of Bioanalytical Chemistry , Tohoku Pharmaceutical University , Miyagi ;
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Fujimura
authors.affiliation: f Laboratory of Molecular and Biochemical Research , Research Support Center, Juntendo University , Tokyo ;
authors.forename: Takako
authors.initials: T
authors.lastname: Ikegami
authors.affiliation: g Graduate School of Pharmaceutical Sciences , Tohoku University , Miyagi ;
authors.forename: Keita
authors.initials: K
authors.lastname: Nakanaga
authors.affiliation: g Graduate School of Pharmaceutical Sciences , Tohoku University , Miyagi ;
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Matsumoto
authors.affiliation: d BioMedical Research Center, Juntendo University , Tokyo ;
authors.forename: Takashi
authors.initials: T
authors.lastname: Ueno
authors.affiliation: g Graduate School of Pharmaceutical Sciences , Tohoku University , Miyagi ;
authors.forename: Junken
authors.initials: J
authors.lastname: Aoki
authors.affiliation: h Department of Biochemistry (I) , Juntendo University , Tokyo , Japan ;
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokomizo
authors.affiliation: i Department of Leukemia , the University of Texas MD Anderson Cancer Center , Houston , Texas , USA ;
authors.forename: Marina
authors.initials: M
authors.lastname: Konopleva
authors.affiliation: i Department of Leukemia , the University of Texas MD Anderson Cancer Center , Houston , Texas , USA ;
authors.forename: Michael
authors.initials: M
authors.lastname: Andreeff
authors.affiliation: a Department of Laboratory Medicine , Juntendo University , Tokyo ;
authors.forename: Takashi
authors.initials: T
authors.lastname: Miida
authors.affiliation: j Research Institute for Environmental and Gender Specific Medicine, Juntendo University , Tokyo , Japan .
authors.forename: Kazuhisa
authors.initials: K
authors.lastname: Iwabuchi
authors.affiliation: b Department of Radiology , Juntendo University , Tokyo ;
authors.forename: Keisuke
authors.initials: K
authors.lastname: Sasai
mesh_terms: D001402:B-Lymphocytes / Q000502:physiology* / Q000528:radiation effects / Q000821:virology*; D002460:Cell Line; D004307:Dose-Response Relationship, Radiation; D015971:Gene Expression Regulation, Enzymologic / Q000502:physiology* / Q000528:radiation effects; D023281:Genomics / Q000379:methods*; D005992:Glycerol-3-Phosphate O-Acyltransferase / Q000378:metabolism*; D004854:Herpesvirus 4, Human / Q000502:physiology* / Q000528:radiation effects; D006801:Humans; D011829:Radiation Dosage; D018511:Systems Integration
chemical_list: D005992:Glycerol-3-Phosphate O-Acyltransferase
keywords: Epstein-Barr virus-infected B-cells (EBV-B); Low-dose ionizing radiation (LDIR); glycerol-3-phosphate acyltransferase (GPAM); isobaric tags for relative and absolute quantification (iTRAQ); microRNA (miRNA)