MicroRNAs (
miRNAs) regulate gene expression by forming
RNA-induced silencing complexes (RISCs) and have been considered as promising therapeutic targets.
MiRNA is an essential component of RISC for the modulation of gene expression. Therefore, the release of
miRNA from RISC is considered as an effective method for the inhibition of
miRNA functions. In our previous study, we reported that anti-
miRNA oligonucleotides (AMOs), which are composed of the 2'-O-methyl (2'-OMe)
RNA, could induce the release of
miRNA from RISC. However, the mechanisms underlying the
miRNA-releasing effects of chemically modified AMOs, which are conventionally used as anti-
cancer drugs, are still unclear. In this study, we investigated the relationship between the
miRNA releasing rate from RISC and the inhibitory effect on RISC activity (IC50) using conventional chemically modified AMOs. We demonstrated that the
miRNA-releasing effects of AMOs are directly proportional to the IC50 values, and AMOs, which have an ability to promote the release of
miRNA from RISC, can effectively inhibit RISC activity in living cells.