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Early research in developmental timing in C. elegans led to the discovery of lin-4, the first microRNA gene (Lee 1993, Wightman 1993). Since then, miRNAs have been implicated in developmental processes including embryogenesis, differentiation, developmental timing, organogenesis, growth control, and programmed cell death (see Alvarez-Garcia 2005 for a review). Current interest in miRNA regulation of human embryonic stem cells.
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Altered expression of particular miRNAs has been implicated in the onset and development of cancer; although it remains unclear the specific role of miRNAs in derangement of cellular mechanisms. miRNAs are thought to function in tumor suppression and as oncogenes. Early studies identified that nearly half of microRNA genes reside in cancer-associated genomic regions (Calin 2004). Further studies (Lu et al. 2005) show that disruption of the microRNA profile occurs in cancers, and over expression resulting from the disruption may lead to the development of tumors (He et al. 2005). Changes in miRNA expression have been identified as potential biomarkers for disease diagnosis (Croce 2006).
Calin, G.A. and Croce, C.M. MicroRNA Signatures in Human Cancers. Nature Reviews Cancer. 2006; 6(11):857-66.
Lu, J., et al. MicroRNA Expression Profiles Classify Human Cancers. Nature. 2005; 435, 834–838.
Mattick, JS. A New Paradigm for Developmental Biology. Journal of Experimental Biology. May 2007; 210: 1526 - 1547.
Alvarez-Garcia I. and Miska, EA. MicroRNA Functions in Animal Development and Human Disease. Development. 2005; 132 (21): .4653-4662.
Calin, G.A., et al. MicroRNA Profiling Reveals Distinct Signatures in B Cell Chronic Lymphocytic Leukemias. Proc. Natl Acad. Sci. 2004; 101: 11755–11760.
Croce, MA., et. al. MicroRNA Expression Abnormalities in Pancreatic Endocrine and Acinar Tumors Are Associated With Distinctive Pathologic Features and Clinical Behavior. Journal of Clinical Oncology. 2006; 24: 4677-4684.
He, L., et al. A microRNA Polycistron as a Potential Human Oncogene. Nature 2005; 435: 828-833.
Lecellier, C.H., et. al. A Cellular microRNA Mediates Antiviral Defense in Human Cells. Science. 2005; 308: 557–560.
Lee, RC., et. al. The C. elegans Heterochronic Gene lin-4 Encodes Small RNAs with Antisense Complementarity to lin-14. Cell. 1993;75: 843 -854.
Lu, J., et al. MicroRNA Expression Profiles Classify Human Cancers. Nature. 2005; 435: 834–838.
Wightman, B., et. al. Posttranscriptional Regulation of the Heterochronic Gene lin-14 by lin-4 Mediates Temporal Pattern Formation in C. elegans. Cell. 1993; 75: 855 -862.
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