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

• We generated pyrrole–imidazole (PI) polyamides that could bind to an E-box motif.
• PI polyamide Myc-6 induces G1 arrest and apoptosis in human osteosarcoma MG63 cells.
• Myc-6 represses tumor growth both in vitro and in vivo.
• Myc-6 binds to the 5′-upstream region of noncoding RNA MALAT1 and reduces its expression.
• Myc-6 exerts its tumor-suppressive ability through the down-regulation of MALAT1.

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.