FEBS Open Bio
(Jan 2014)
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
Affiliations
Masashi Taniguchi
Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan
Kyoko Fujiwara
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan
Yuji Nakai
Graduate School of Agricultural and Life Sciences, The University of Tokyo, Japan
Toshinori Ozaki
Laboratory of DNA Damage Signaling, Chiba Cancer Center Research Institute, Japan
Nobuko Koshikawa
Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Japan
Kojima Toshio
Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan
Motoaki Kataba
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan
Asako Oguni
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan
Hiroyuki Matsuda
Division of General Medicine, Department of Internal Medicine, Nihon University School of Medicine, Japan
Yukihiro Yoshida
Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan
Yasuaki Tokuhashi
Division of Orthopedic Surgery, Nihon University School of Medicine, 30-1 Oyaguchi Kami-Cho, Itabashi, Tokyo 173-8610, Japan
Noboru Fukuda
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan
Takahiro Ueno
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan
Masayoshi Soma
Innovative Therapy Research Group, Nihon University Research Institute of Medical Science, Nihon University School of Medicine, Japan
Hiroki Nagase
Laboratory of Cancer Genetics, Chiba Cancer Center Research Institute, Japan
DOI
https://doi.org/10.1016/j.fob.2014.03.004
Journal volume & issue
Vol. 4,
no. C
pp.
328
– 334
Abstract
Read online
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.
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