Development of a novel nucleic acid drug targeting sense/antisense transcript pairs

最近的研究表明，与靶基因启动子区域互补的小双链RNA可以增强靶基因的表达。这种现象被称为“RNA激活”。在本研究中，我们检测了与RECK基因启动子互补的小双链RNA(DsRNA)能否激活培养的肿瘤细胞系中基质金属蛋白酶(MMPs)抑制剂RECK的表达，从而抑制MMPs的表达，从而抑制肿瘤细胞的侵袭。转导dsRNAs后，RECK在人类肿瘤细胞中的表达水平显著提高了约6倍。此外，dsRNA诱导的RECK表达上调导致MMPs表达减少，从而导致肿瘤细胞的侵袭。这些结果表明，与抑癌基因启动子区域互补的小分子双链RNA有可能成为一种新型的抗肿瘤药物。

Recent studies have demonstrated that small duplex RNA complementary to the promoter region of target gene enhances expression of target genes. This phenomenon is designated as “RNA activation”. In this study, we examined whether expression of the matrix metalloproteinase (MMP) inhibitor RECK is activated in the cultured tumor cell lines by transfection with small duplex RNA (dsRNA) complementary to the promoter of RECK gene, leading to the suppression of expression of MMPs and invasion of the tumor cells. Transfection with the dsRNAs significantly elevated RECK expression levels by approximately 6-fold in human tumor cells. Furthermore, the dsRNA-induced elevation of RECK expression resulted in reduction in expression of MMPs and invasion of tumor cells. These results suggest that small duplex RNA complementary to the promoter region of tumor suppressor genes would have the potential as a novel antitumor agent.