Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif

Masashi Taniguchi; Kyoko Fujiwara; Yuji Nakai; Toshinori Ozaki; Nobuko Koshikawa; Kojima Toshio; Motoaki Kataba; Asako Oguni; Hiroyuki Matsuda; Yukihiro Yoshida; Yasuaki Tokuhashi; Noboru Fukuda; Takahiro Ueno; Masayoshi Soma; Hiroki Nagase

doi:10.1016/j.fob.2014.03.004

Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif

FEBS Open Bio. 2014 Mar 13:4:328-34. doi: 10.1016/j.fob.2014.03.004. eCollection 2014.

Authors

Affiliations

¹ Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan.
² Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan ; Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, Japan.
³ Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
⁴ Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Japan.
⁵ Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Japan.
⁶ Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan.
⁷ Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, Japan.
⁸ Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan ; Division of Nephrology, Hypertension and Endocrinology, Department of Medicine, Nihon University School of Medicine, Japan.

Abstract

Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to the E-box sequence (5'-CACGTG-3'), has been observed in many human tumors. In this study, we have designed 5 pyrrole-imidazole (PI) polyamides recognizing E-box, and found that, among them, Myc-6 significantly suppresses malignant phenotypes of human osteosarcoma MG63 cells both in vitro and in vivo. Intriguingly, knockdown of the putative Myc-6 target MALAT1 encoding long noncoding RNA remarkably impaired cell growth of MG63 cells. Collectively, our present findings strongly suggest that Myc-6 exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.

Keywords: E-box; MALAT1; MG63 cells; Osteosarcoma; PI polyamide, pyrrole–imidazole polyamide; Pyrrole–imidazole polyamide; c-MYC.