MicroRNAs in carcinogenesisHagan J.P. · Croce C.M.
Comprehensive Cancer Center, The Ohio State University Medical Center, Columbus, OH (USA)
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MicroRNAs are an abundant class of noncoding RNAs, typically 20–23 nucleotides in length that are often evolutionarily conserved in metazoans and expressed in a cell and tissue specific manner. MicroRNAs exert their gene regulatory activity primarily by imperfectly base pairing to the 3′ UTR of their target mRNAs, leading to mRNA degradation or translational inhibition. In cancer, microRNAs are often dysregulated with their expression patterns being correlated with clinically relevant tumor characteristics. Recently, microRNAs were shown to be directly involved in cancer initiation and progression. This review focuses primarily on emerging developments in the microRNA field that impact our understanding of how these molecules contribute to carcinogenesis.
© 2007 S. Karger AG, Basel
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Since the acceptance of this review, many important papers have been published in relation to mammalian microRNA biology. For brevity’s sake, a few noteworthy studies in the context of this review will be mentioned. MicroRNA-125a/b whose expression is frequently lost or reduced in breast cancer has been reported to regulate the important oncogenes ERBB2 and ERBB3 (Scott et al., 2007). Two research groups have published a mouse knockout of miR-155, demonstrating that this microRNA is required for normal immune function (Rodriguez et al., 2007; Thai et al., 2007). Similarly, a mouse knockout of miR-1-2 is characterized by cardiac defects, leading to 50% lethality by weaning age (Zhao et al., 2007). Lastly, mouse screens that involve mapping of retroviral integration sites that lead to T-cell lymphoma development have identified the activation of two separate microRNA clusters, miR-17/18/19a/ 20a/19b-1/92-1 or miR-106a/20b/19b-2/92-2/ 363, as the causative event (Wang et al., 2006; Lum et al., 2007). These results confirm the significance of microRNAs in normal mammalian development and in cancer.
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