MicroRNA profiling identifies miR-34a and miR-21 and their target genes JAG1 and WNT1 in the coordinate regulation of dendritic cell differentiation

摘要: MicroRNAs (miRNAs, miRs) modulate a multitude of cellular events. Here, we identify functional miRNA-protein networks that regulate human monocyte-derived dendritic cell (MDDC) differentiation. miRNA profiling revealed stage-specific differential expression 20 miRNAs during days 1, 3, and 5 MDDC To prioritize for validation, developed target ranking algorithm incorporates many features regulatory networks. This system prioritized miR-21, miR-34a, their cognate targets WNT1 JAG1 validation. Inhibition both miR-21 miR-34a stalled differentiation, as quantified by DC-SIGN/CD14 ratios, showing cooperative involvement these in We confirmed the 3′ untranslated regions were provide evidence translationally suppressed. Significantly, exogenously added Wnt-1 Jagged-1 also suggesting miRNA-mediated inhibition endogenous was important proper Finally, or addition Jagged-1, led to decrease endocytic capacity, key function immature DCs. Thus, our novel approach identified validated some involved phenotypic