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

• Main Authors: 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
• Format: Article
• Language: English
• Published: Wiley 2014-01-01
• Series: FEBS Open Bio
• Subjects: c-MYC; E-box; MALAT1; MG63 cells; Osteosarcoma; Pyrrole–imidazole polyamide
• Online Access: http://www.sciencedirect.com/science/article/pii/S2211546314000278

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.