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

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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.