MicroRNAs in the miR-106b Family Regulate p21/CDKN1A and Promote Cell Cycle Progression

作者：Irena L. Ivanovska, Alexey Ball, Robert L. Diaz, Jill Magnus, Miho Kibukawa, Janell M. Schelter, Sumire Kobayashi, Lee P. Lim, Julja Burchard, Aimee L. Jackson, Peter S. Linsley, Michele A. Cleary · 发表于：Molecular and Cellular Biology · 年份：2008 · DOI：10.1128/mcb.01977-07 · 被引用次数：557 · 研究领域：MicroRNA in disease regulation、Circular RNAs in diseases、Cancer-related molecular mechanisms research

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.