Transcriptional Regulation Of Dicer By FoxO3

MicroRNAs(miRNA)are a class of endogenous small non-protein coding RNAs(16-29 nucleotides long)that interact with target mRNAs in a sequence-specific manner as a part of the RNA interference silencing complex(RISC)and,by doing so,they can regulate gene expression at a post-transcriptional level.Recent evidence has shown that miRNA mutations or mis-expression correlate with various human cancers and indicates that miRNAs can function as tumour suppressors and oncogenes.Dicer,the highly conserved and specialized eukaryotic RNase,acts on double-stranded RNA(dsRNA)substrates from varied origins to produce small interfering RNAs(siRNAs)of discrete sizes,which in turn proceed to direct the sequence specificity of gene silencing through RNAi.As a very important transcription factor,Fox03 is involved in the regulation of cell cycle regulation,DNA damage repair,apoptosis,cell differentiation,anti-oxidative stress,cell metabolism,stem cell homeostasis and cell death through transcriptional regulation of downstream target genes.Here,we report that Fox03 directs the basal transcription of Dicer and Fox03 depletion results in Dicer down-regulation through a series of analysis.Importantly,Fox03 silencing led to decreased mature miRNA expression,in a Dicer-dependent manner.Conclusion;Our results unravel a unique mechanism underlying the potential function of Fox03 through influncing the biogenesis of mature miRNA processed by Dicer.Large-scale expression screens will be useful in identifying novel miRNAs that are involved in cancer and cancer-related processes such as cell proliferation and apoptosis.