predicted by different computational target prediction algorithms. Seven proteins (cyclins Ccnd2, Ccnd3, and Ccne1, and cyclin-dependent kinases Cdk4, Cdk6, Chk1, and Mcm5) known to be involved in the regulation of the G0/G1-S phase transition, were downregulated in I83E95 13q14−/− cells upon miR-15a/16-1 expression. Similarly, the same gene products showed higher expression levels in anti-IgM-stimulated miR-15a/16-1-deficient mouse B cells. Though it remains to be determined whether the proliferation-associated genes identified represent direct or indirect miR-15a/16-1 targets, the concurrent results obtained in two independent genetically defined miR-15a/16-1 knockout systems strongly indicate that these miRNAs regulate the expression of multiple genes involved in the G0/G1-S phase transition in both human and mouse B cells [56, 57].
