let-7Overexpression Leads to an Increased Fraction of Cells in G2/M, Direct Down-regulation of Cdc34, and Stabilization of

microRNAs play a critically important role in a wide array of biological processes including those implicated in cancer, neuro-degenerative and metabolic disorders, and viral infection. Althoughwe have begun to understandmicroRNAbiogenesis and function, experimental demonstration of their functional effects and the molecular mechanisms by which they function remains a challenge.Membersof the let-7/miR-98 familyplayacritical role in cell cycle controlwith respect todifferentiationand tumorigenesis. In this study, we show that exogenous addition of pre-let-7 in pri-maryhuman fibroblasts results in a decrease in cell number and an increased fraction of cells in theG2/M cell cycle phase. Combining microarray techniques with DNA sequence analysis to identify potential let-7 targets,wediscovered838geneswitha let-7binding site in their 3-untranslated region thatweredown-regulatedupon overexpression of let-7b. Among these genes is cdc34, the ubiq