Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma

Tsuyoshi Ueno; Shinichi Toyooka; Takuya Fukazawa; Takafumi Kubo; Junichi Sou; Hiroaki Asano; Takayuki Muraoka; Norimitsu Tanaka; Yuho Maki; Kazuhiko Shien; Masashi Furukawa; Masakiyo Sakaguchi; Hiromasa Yamamoto; Kazunori Tsukuda; Shinichiro Miyoshi

Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma

Tsuyoshi Ueno, Shinichi Toyooka, Takuya Fukazawa, Takafumi Kubo, Junichi Sou, Hiroaki Asano, Takayuki Muraoka, Norimitsu Tanaka, Yuho Maki, Kazuhiko Shien, Masashi Furukawa, Masakiyo Sakaguchi, Hiromasa Yamamoto, Kazunori Tsukuda, Shinichiro Miyoshi

Research output: Contribution to journal › Article › peer-review

24 Citations (Scopus)

Abstract

The microRNA-34s (miR-34s) have p53 response elements in their 5'-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6? on day 10 and 54.7? on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM.

Original language	English
Pages (from-to)	23-26
Number of pages	4
Journal	Acta medica Okayama
Volume	68
Issue number	1
Publication status	Published - 2014

Keywords

Mesothelioma
MicroRNA
MicroRNA-34b/c
p53

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

Cite this

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title = "Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma",

abstract = "The microRNA-34s (miR-34s) have p53 response elements in their 5'-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6? on day 10 and 54.7? on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM.",

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author = "Tsuyoshi Ueno and Shinichi Toyooka and Takuya Fukazawa and Takafumi Kubo and Junichi Sou and Hiroaki Asano and Takayuki Muraoka and Norimitsu Tanaka and Yuho Maki and Kazuhiko Shien and Masashi Furukawa and Masakiyo Sakaguchi and Hiromasa Yamamoto and Kazunori Tsukuda and Shinichiro Miyoshi",

year = "2014",

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T1 - Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma

AU - Ueno, Tsuyoshi

AU - Toyooka, Shinichi

AU - Fukazawa, Takuya

AU - Kubo, Takafumi

AU - Sou, Junichi

AU - Asano, Hiroaki

AU - Muraoka, Takayuki

AU - Tanaka, Norimitsu

AU - Maki, Yuho

AU - Shien, Kazuhiko

AU - Furukawa, Masashi

AU - Sakaguchi, Masakiyo

AU - Yamamoto, Hiromasa

AU - Tsukuda, Kazunori

AU - Miyoshi, Shinichiro

PY - 2014

Y1 - 2014

N2 - The microRNA-34s (miR-34s) have p53 response elements in their 5'-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6? on day 10 and 54.7? on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM.

AB - The microRNA-34s (miR-34s) have p53 response elements in their 5'-flanking regions and demonstrate tumor-suppressive functions. In malignant pleural mesothelioma (MPM), we previously reported that expression of miR-34b and miR-34c (miR-34b/c) was frequently downregulated by methylation in MPM cell lines and primary tumors. The forced overexpression of miR-34b/c showed significant antitumor effects with the induction of apoptosis in MPM cells. In this study, we examined the in vivo antitumor effects of miR-34b/c using adenovirus vector on MPM. We subcutaneously transplanted NCI-H290, a human MPM cell line, into BALB/C mice and injected adenovirus vector expressing miR-34b/c, luciferase driven by the cytomegalovirus promoter (Ad-miR-34b/c or Ad-Luc), or PBS control into tumors over 5mm in diameter. A statistically significant growth inhibition of the tumor volume was observed in the Ad-miR-34b/c group from day 6 onward compared to the Ad-Luc group. The inhibition rate of Ad-miR-34b/c, compared to the tumor volume treated with Ad-Luc, was 58.6? on day 10 and 54.7? on day13. Our results indicate that adenovirus-mediated miR-34b/c gene therapy could be useful for the clinical treatment of MPM.

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Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma

Abstract

Keywords

ASJC Scopus subject areas

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