MicroRNAs in the miR-106b family regulate p21/CDKN1A and promote cell cycle progression |
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| Authors: | Ivanovska Irena Ball Alexey S Diaz Robert L Magnus Jill F Kibukawa Miho Schelter Janell M Kobayashi Sumire V Lim Lee Burchard Julja Jackson Aimee L Linsley Peter S Cleary Michele A |
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| Affiliation: | Rosetta Inpharmatics LLC, Seattle, Washington 98109 |
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| Abstract: | microRNAs in the miR-106b family are overexpressed 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 that 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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