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

Yuho Maki, Hiroaki Asano, Shinichi Toyooka, Junichi Sou, 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 journalArticle

19 Citations (Scopus)

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

Fingerprint

Radiation Tolerance
MicroRNAs
Cyclin-Dependent Kinase 6
Cyclin-Dependent Kinase 4
Malignant Mesothelioma
Double-Stranded DNA Breaks
Poly(ADP-ribose) Polymerases
Cyclin D1
G1 Phase
B-Cell Lymphoma
Epigenomics
Caspase 3
Histones
Cell Cycle
Radiotherapy
Western Blotting
Radiation
Apoptosis
Cell Line

Keywords

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

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural mesothelioma cells. / Maki, Yuho; Asano, Hiroaki; Toyooka, Shinichi; Sou, Junichi; Kubo, Takafumi; Katsui, Kuniaki; Ueno, Tsuyoshi; Shien, Kazuhiko; Muraoka, Takayuki; Tanaka, Norimitsu; Yamamoto, Hiromasa; Tsukuda, Kazunori; Kishimoto, Takumi; Kanazawa, Susumu; Miyoshi, Shinichiro.

In: Anticancer Research, Vol. 32, No. 11, 11.2012, p. 4871-4876.

Research output: Contribution to journalArticle

Maki, Y, Asano, H, Toyooka, S, Sou, J, Kubo, T, Katsui, K, Ueno, T, Shien, K, Muraoka, T, Tanaka, N, Yamamoto, H, Tsukuda, K, Kishimoto, T, Kanazawa, S & Miyoshi, S 2012, 'MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural mesothelioma cells', Anticancer Research, vol. 32, no. 11, pp. 4871-4876.
Maki, Yuho ; Asano, Hiroaki ; Toyooka, Shinichi ; Sou, Junichi ; Kubo, Takafumi ; Katsui, Kuniaki ; Ueno, Tsuyoshi ; Shien, Kazuhiko ; Muraoka, Takayuki ; Tanaka, Norimitsu ; Yamamoto, Hiromasa ; Tsukuda, Kazunori ; Kishimoto, Takumi ; Kanazawa, Susumu ; Miyoshi, Shinichiro. / MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural mesothelioma cells. In: Anticancer Research. 2012 ; Vol. 32, No. 11. pp. 4871-4876.
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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.",
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AU - Maki, Yuho

AU - Asano, Hiroaki

AU - Toyooka, Shinichi

AU - Sou, Junichi

AU - Kubo, Takafumi

AU - Katsui, Kuniaki

AU - Ueno, Tsuyoshi

AU - Shien, Kazuhiko

AU - Muraoka, Takayuki

AU - Tanaka, Norimitsu

AU - Yamamoto, Hiromasa

AU - Tsukuda, Kazunori

AU - Kishimoto, Takumi

AU - Kanazawa, Susumu

AU - Miyoshi, Shinichiro

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N2 - 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.

AB - 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.

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