title: MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural mesothelioma cells.
abstract: BACKGROUND
  We previously reported that epigenetic silencing of microRNA-34b/c (miR-34b/c) plays an important role in the pathogenesis of malignant pleural mesothelioma (MPM). We examined the impact of miR-34b/c restoration on the radiosensitivity of MPM cells.
  
  
  METHODS
  We established stable miR-34b/c and scramble transfectants of two MPM cell lines, H2052 and H28. We examined these transfectants by clonogenic survival assay, phosphorylated histone H2AX (γH2AX) foci assay, cell-cycle analysis, and western blotting.
  
  
  RESULTS
  The clonogenic survival assay revealed that miR-34b/c radiosensitized MPM cells. γH2AX foci assay showed that DNA double-strand break repair was delayed in miR-34b/c transfectants. The proportion of sub-G(1) phase cells was increased in miR-34b/c transfectants after irradiation. miR-34b/c inhibited expression of cyclin-D1, cyclin-dependent kinase 4/6, B-cell lymphoma-2 (BCL-2) and increased cleaved poly (ADP-ribose) polymerase (cPARP) and cleaved caspase-3 after irradiation.
  
  
  CONCLUSIONS
  Our results indicate that miR-34b/c enhances radiosensitivity by promoting radiation-induced apoptosis and suggested that miR-34b/c might be a useful therapeutic molecule to enhance radiotherapy in MPM.
authors.affiliation: Department of Thoracic Surgery, Okayama University Hospital, 2-5-1 Shikata-cho, Kita-ku, Okayama 700-8558, Japan.
authors.forename: Yuho
authors.initials: Y
authors.lastname: Maki
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Asano
authors.forename: Shinichi
authors.initials: S
authors.lastname: Toyooka
authors.forename: Junichi
authors.initials: J
authors.lastname: Soh
authors.forename: Takafumi
authors.initials: T
authors.lastname: Kubo
authors.forename: Kuniaki
authors.initials: K
authors.lastname: Katsui
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Ueno
authors.forename: Kazuhiko
authors.initials: K
authors.lastname: Shien
authors.forename: Takayuki
authors.initials: T
authors.lastname: Muraoka
authors.forename: Norimitsu
authors.initials: N
authors.lastname: Tanaka
authors.forename: Hiromasa
authors.initials: H
authors.lastname: Yamamoto
authors.forename: Kazunori
authors.initials: K
authors.lastname: Tsukuda
authors.forename: Takumi
authors.initials: T
authors.lastname: Kishimoto
authors.forename: Susumu
authors.initials: S
authors.lastname: Kanazawa
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Miyoshi
mesh_terms: D017209:Apoptosis / Q000235:genetics; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics; D045744:Cell Line, Tumor; D005455:Fluorescent Antibody Technique; D006801:Humans; D008654:Mesothelioma / Q000235:genetics*; D035683:MicroRNAs / Q000235:genetics*; D010997:Pleural Neoplasms / Q000235:genetics*; D011836:Radiation Tolerance / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D014162:Transfection
chemical_list: C522425:MIRN34 microRNA, human; D035683:MicroRNAs