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Mol. Cell. Biol. doi:10.1128/MCB.01977-07
Copyright (c) 2008, American Society for Microbiology and/or the Listed Authors/Institutions. All Rights Reserved.

MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression

Rosetta Inpharmatics, LLC, a wholly owned subsidiary of Merck and Co. Inc., Seattle, WA 98109

^* To whom correspondence should be addressed. Email: irena_ivanovska{at}merck.com.

	Abstract

microRNAs in the miR-106b family are over-expressed in multiple tumor types and are correlated with the expression of genes that regulate the cell cycle. Consistent with these observations, miR-106b family gain-of-function promotes cell-cycle progression, whereas loss-of-function reverses this phenotype. Microarray profiling uncovers multiple targets of the family including the cyclin-dependent kinase inhibitor p21/CDKN1A. We show that p21 is a direct target of miR-106b and its silencing plays a key role in miR-106b-induced cell-cycle phenotypes. We also show that miR-106b overrides a doxorubicin-induced DNA damage checkpoint. Thus, miR-106b family members contribute to tumor cell proliferation in part by regulating cell cycle progression and by modulating checkpoint functions.

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