Checks and balances: E2F-microRNA crosstalk in cancer control

Extensive research on the E2F transcription factor family over the past decades has led to numerous insights that revealed the involvement of particularly E2F1 not only in proliferation and tumorigenesis but also in apoptosis and differentiation. Latest reports uncovered an essential role for oncogene signaling in regulating the balance of these events on the road to malignancy. Alterations in E2F functions coincide with poor prognosis in cancers, emphasizing their importance for the clinical cancer phenotype. An intriguing addition to the understanding of E2F crosstalks was the finding that their activity can be regulated by micro-RNAs (miRNAs) whose dysregulation has been implicated in malignancy. In turn, miRNAs themselves are targets of E2F family proteins establishing negative feedback loops. Since individual miRNAs may regulate hundreds of genes, these findings add a new challenging layer of complexity to the E2F network that possibly helps to make cell fate decisions. This review outlines our current understanding of the checks and balances of E2Fs and microRNAs in the context of a seemingly paradoxical role in cancer control.