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MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural mesothelioma cells

  • Yuho Maki
  • , Hiroaki Asano
  • , Shinichi Toyooka
  • , Junichi Soh
  • , Takafumi Kubo
  • , Kuniaki Katsui
  • , Tsuyoshi Ueno
  • , Kazuhiko Shien
  • , Takayuki Muraoka
  • , Norimitsu Tanaka
  • , Hiromasa Yamamoto
  • , Kazunori Tsukuda
  • , Takumi Kishimoto
  • , Susumu Kanazawa
  • , Shinichiro Miyoshi

Research output: Contribution to journalArticlepeer-review

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. Materials and 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-G1 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. Conclusion: 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.

Original languageEnglish
Pages (from-to)4871-4876
Number of pages6
JournalAnticancer research
Volume32
Issue number11
Publication statusPublished - Nov 2012

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

  1. SDG 3 - Good Health and Well-being
    SDG 3 Good Health and Well-being

Keywords

  • Malignant pleural mesothelioma
  • MiR-34b/c
  • Radiation
  • Radiosensitivity
  • microRNA

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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