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MicroRNAs (miRNAs) are known to be important post-transcription regulators of gene expression. Aberrant miRNA expression is associated with pathological disease processes, including carcinogenesis. Therefore, miRNAs are considered significant therapeutic targets for cancer therapy. MiRNAs do not act alone, but exhibit their functions by forming RNA-induced silencing complex (RISC). Thus, the regulation of RISC activity is a promising approach for cancer therapy. MiRNA is a core component of RISC and is an essential to RISC for recognizing target mRNA. Thereby, it is expected that development of the method to promote the release of miRNA from RISC would be an effective approach for inhibition of RISC activity. In this study, we synthesized novel peptide-conjugated oligonucleotides (RINDA-as) to promote the release of miRNA from RISC. RINDA-as showed a high rate of miRNA release from RISC and high level of inhibitory effect on RISC activity.

MicroRNAs (miRNAs) are short non-coding RNAs, which play important roles in many biological functions in multicellular organisms. In recent reports, aberrant expressions of miRNAs in several pathological processes, including those in cancers, have been described. Therefore, miRNAs have been considered as promising therapeutic targets. The miRNA duplex associates with the Argonaute protein (Ago) to form ribonucleoprotein complexes called RNA-induced silencing complex (RISC). MiRNA is a core component of RISC and is an essential to RISC for recognizing target mRNA. Thereby, it is expected that development of the method to promote the release of miRNA from RISC would be an effective approach for inhibition of RISC activity. This study presents development of the novel anti-miRNA oligonucleotides (AMOs) to promote the release of miRNA from RISC.