MicroRNAs and the cell cycle.

The control of cell proliferation by microRNAs (miRNAs) is well established and the alteration of these small, non-coding RNAs may contribute to tumor development by perturbing critical cell cycle regulators. Oncogenic miRNAs may facilitate cell cycle entry and progression by targeting CDK inhibitors or transcriptional repressors of the retinoblastoma family. On the other hand, tumor suppressor miRNAs induce cell cycle arrest by downregulating multiple components of the cell cycle machinery. Recent data also suggest that miRNAs act co-ordinately with transcriptional factors involved in cell cycle regulation such as c-MYC, E2F or p53. These miRNAs not only can potentiate the function of these factors but they may also limit the excessive translation of cell cycle proteins upon mitogenic or oncogenic stimuli to protect cells from replicative stress. The implications of these regulatory networks in cell proliferation and human disease are discussed.