The Regulation and Functions of Mammalian MicroRNAs

MicroRNA (miRNA) gain- and loss-of-function can potently influence cellular behavior in normal physiologic states and in diseases such as cancer.  The regulation of miRNA expression and activity by cellular signaling cascades can therefore result in dramatic phenotypic outputs.  We previously demonstrated extensive control of miRNA expression by well-characterized oncogenic and tumor suppressor networks including the Myc, Kras, and p53 pathways.  We are now employing novel mouse models with gain and loss of miRNA function to investigate the physiologic functions of the miRNAs embedded within these signaling pathways and the pathologic consequences when their functions are disrupted.  Insights gained from these studies are revealing unanticipated roles for miRNAs in vivo and are informing our understanding of how dysregulated miRNA activity contributes to tumorigenesis.  I will present our latest findings related to the regulation and function of mammalian miRNAs in normal physiology and in cancer and how these findings may be exploited for the development of novel therapeutic approaches.