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

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16 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 languageEnglish
Pages (from-to)23-26
Number of pages4
JournalActa Medica Okayama
Volume68
Issue number1
Publication statusPublished - 2014

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Keywords

  • Mesothelioma
  • MicroRNA
  • MicroRNA-34b/c
  • p53

ASJC Scopus subject areas

  • Medicine(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Ueno, T., Toyooka, S., Fukazawa, T., Kubo, T., Sou, J., Asano, H., Muraoka, T., Tanaka, N., Maki, Y., Shien, K., Furukawa, M., Sakaguchi, M., Yamamoto, H., Tsukuda, K., & Miyoshi, S. (2014). Preclinical Evaluation of MicroRNA-34b/c Delivery for Malignant Pleural Mesothelioma. Acta Medica Okayama, 68(1), 23-26.