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

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

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24 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 language	English
Pages (from-to)	4871-4876
Number of pages	6
Journal	Anticancer research
Volume	32
Issue number	11
Publication status	Published - Nov 2012

Keywords

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

ASJC Scopus subject areas

Oncology
Cancer Research

UN SDGs

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

Cite this

@article{456c4ea9564f4c028c9aabfa003d4963,

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. 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.",

keywords = "Malignant pleural mesothelioma, MiR-34b/c, Radiation, Radiosensitivity, microRNA",

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

year = "2012",

month = nov,

language = "English",

volume = "32",

pages = "4871--4876",

journal = "Anticancer Research",

issn = "0250-7005",

publisher = "International Institute of Anticancer Research",

number = "11",

}

TY - JOUR

T1 - MicroRNA miR-34b/c enhances cellular radiosensitivity of malignant pleural mesothelioma cells

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

PY - 2012/11

Y1 - 2012/11

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.

KW - Malignant pleural mesothelioma

KW - MiR-34b/c

KW - Radiation

KW - Radiosensitivity

KW - microRNA

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M3 - Article

C2 - 23155254

AN - SCOPUS:84872648141

SN - 0250-7005

VL - 32

SP - 4871

EP - 4876

JO - Anticancer Research

JF - Anticancer Research

IS - 11

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

UN SDGs

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