Mouse miR-290 cluster miRNAs are expressed specifically in early embryos and embryonic germ cells.These miRNAs play critical roles in the maintenance of pluripotency and self-renewal.Here,we showed that Cyclin D1 is a direct target gene of miR-290 cluster miRNAs.Negative relationships between the expression of Cyclin D1 protein and miR-290 cluster miRNAs in pluripotent and non-pluripotent cells,as well as in differentiating CGR8 cells were observed.Inhibition of miR-290 cluster miRNAs could arrest cells at the G1 phase and slow down the cell proliferation in CGR8 mouse stem cells.Since miR-290 cluster miRNAs are the most dominant stem-cell-specific miRNAs,our results revealed an important cause for the absence of Cyclin D1 in mouse embryonic stem cells.