title: Inhibition of malignant phenotypes of human osteosarcoma cells by a gene silencer, a pyrrole-imidazole polyamide, which targets an E-box motif.
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.
authors.affiliation: Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Taniguchi
authors.affiliation: 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.
authors.forename: Kyoko
authors.initials: K
authors.lastname: Fujiwara
authors.affiliation: Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Nakai
authors.affiliation: Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Japan.
authors.forename: Toshinori
authors.initials: T
authors.lastname: Ozaki
authors.affiliation: Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Japan.
authors.forename: Nobuko
authors.initials: N
authors.lastname: Koshikawa
authors.affiliation: Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan.
authors.forename: Kojima
authors.initials: K
authors.lastname: Toshio
authors.affiliation: Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan.
authors.forename: Motoaki
authors.initials: M
authors.lastname: Kataba
authors.affiliation: Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan.
authors.forename: Asako
authors.initials: A
authors.lastname: Oguni
authors.affiliation: Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Matsuda
authors.affiliation: Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan.
authors.forename: Yukihiro
authors.initials: Y
authors.lastname: Yoshida
authors.affiliation: Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan.
authors.forename: Yasuaki
authors.initials: Y
authors.lastname: Tokuhashi
authors.affiliation: 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.
authors.forename: Noboru
authors.initials: N
authors.lastname: Fukuda
authors.affiliation: 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.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Ueno
authors.affiliation: 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.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Soma
authors.affiliation: Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Japan.
authors.forename: Hiroki
authors.initials: H
authors.lastname: Nagase
keywords: E-box; MALAT1; MG63 cells; Osteosarcoma; PI polyamide, pyrrole–imidazole polyamide; Pyrrole–imidazole polyamide; c-MYC