Role of p27kip1 in the regulation of miR-223 following contact inhibition

microRNAs (also called miRs or miRNAs) are a large class of small regulatory RNAs that function as nodes of signaling networks. This implicates that miRs expression has to be finely tuned, as observed during cell cycle progression. Using an expression profiling approach, we provide evidence that the CDK inhibitor p27kip1 regulates miRs expression following cell cycle exit. By using wild type and p27KO cells, harvested in different phases of the cell cycle, we identified several miRs regulated by p27kip1 during the G1 to S phase transition. Among these miRs, miR-223 was a miR specifically upregulated by p27kip1 in G1 arrested cells. During the work of this PhD thesis, we demonstrated that p27kip1 regulates the expression of miR-223, via two distinct mechanisms. First, p27kip1 directly stabilized mature miR-223 expression, acting as a RNA binding protein. Second, p27kip1 controlled E2F1 expression that, in turn, regulated miR-223 promoter activity. The resulting elevated miR-223 levels ultimately participated to cell cycle arrest following contact inhibition.