Analysis of anti-cancer effect of PI polyamide, which suppress MYC downstream genes

基因扩增和/或转录因子c-MYC的过表达，结合E-box （5'-CACGTG-3'）存在于其众多靶基因启动子中，已在许多人类肿瘤中观察到。在本研究中，我们设计了与E-box结合的吡咯-咪唑聚酰胺（pyrorole -midazole polyamides， PIP），并研究了其对人类癌细胞的可能影响。我们发现我们设计的一些PIP显著抑制骨肉瘤细胞MG63和白血病细胞K562的生长。根据我们目前的结果，pip处理的细胞发生凋亡和/或G1阻滞。此外，静脉注射PIP可显著抑制裸鼠mg63源性肿瘤的发展。有趣的是，敲低推测的PIP靶点编码长链非编码RNA的MALAT1显著损害了MG63细胞的细胞生长。总的来说，我们目前的研究结果强烈表明，PIP至少部分通过特异性下调MALAT1来发挥其肿瘤抑制能力。

Gene amplification and/or overexpression of the transcription factor c-MYC, which binds to E-box (5'-CACGTG-3') present within its numerous target gene promoters, has been observed in many human tumors. In this study, we have designed pyrrole-midazole polyamides (PIP), which could bind to E-box, and investigated their possible effects on human cancer cells. We found that some PIP we designed significantly suppressed growth of osteosarcoma cell MG63 and leukemia cell K562. According to our present results, PIP-treated cells underwent apoptosis and/or G1 arrest. Furthermore, intravenous injection of PIP markedly repressed MG63-derived tumor development in nude mice. Intriguingly, knockdown of the putative PIP target MALAT1 encoding long non-coding RNA remarkably impaired cell growth of MG63 cells. Collectively, our present findings strongly suggest that PIP exerts its tumor-suppressive ability at least in part through the specific down-regulation of MALAT1.