PMID- 21355095 OWN - NLM STAT- MEDLINE DCOM- 20110713 LR - 20220408 IS - 1528-0020 (Electronic) IS - 0006-4971 (Print) IS - 0006-4971 (Linking) VI - 117 IP - 16 DP - 2011 Apr 21 TI - miR-221 and miR-155 regulate human dendritic cell development, apoptosis, and IL-12 production through targeting of p27kip1, KPC1, and SOCS-1. PG - 4293-303 LID - 10.1182/blood-2010-12-322503 [doi] AB - Dendritic cells (DCs) are potent antigen-presenting cells derived from hematopoietic progenitor cells and circulating monocytes. To investigate the role of microRNAs (miRNAs) during DC differentiation, maturation, and function, we profiled miRNA expression in human monocytes, immature DCs (imDCs), and mature DCs (mDCs). Stage-specific, differential expression of 27 miRNAs was found during monocyte differentiation into imDCs and mDCs. Among them, decreased miR-221 and increased miR-155 expression correlated with p27(kip1) accumulation in DCs. Silencing of miR-221 or overexpressing of miR-155 in DCs resulted in p27(kip1) protein increase and DC apoptosis. Moreover, mDCs from miR-155(-/-) mice were less apoptotic than those from wild-type mice. Silencing of miR-155 expression had little effect on DC maturation but reduced IL-12p70 production, whereas miR-155 overexpression in mDCs enhanced IL-12p70 production. Kip1 ubiquitination-promoting complex 1, suppressor of cytokine signaling 1, and CD115 (M-CSFR) were functional targets of miR-155. Furthermore, we provide evidence that miR-155 indirectly regulated p27(kip1) protein level by targeting Kip1 ubiquitination-promoting complex 1. Thus, our study uncovered miRNA signatures during monocyte differentiation into DCs and the new regulatory role of miR-221 and miR-155 in DC apoptosis and IL-12p70 production. FAU - Lu, Changming AU - Lu C AD - Pediatric Blood and Marrow Transplantation, University of Minnesota Medical School, Minneapolis, MN 55455, USA. FAU - Huang, Xin AU - Huang X FAU - Zhang, Xiaoxiao AU - Zhang X FAU - Roensch, Kristin AU - Roensch K FAU - Cao, Qing AU - Cao Q FAU - Nakayama, Keiichi I AU - Nakayama KI FAU - Blazar, Bruce R AU - Blazar BR FAU - Zeng, Yan AU - Zeng Y FAU - Zhou, Xianzheng AU - Zhou X LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20110225 PL - United States TA - Blood JT - Blood JID - 7603509 RN - 0 (CDKN1B protein, human) RN - 0 (MIRN155 microRNA, human) RN - 0 (MIRN221 microRNA, human) RN - 0 (MicroRNAs) RN - 0 (SOCS1 protein, human) RN - 0 (Suppressor of Cytokine Signaling 1 Protein) RN - 0 (Suppressor of Cytokine Signaling Proteins) RN - 147604-94-2 (Cyclin-Dependent Kinase Inhibitor p27) RN - 187348-17-0 (Interleukin-12) RN - 82115-62-6 (Interferon-gamma) RN - EC 2.3.2.27 (RNF123 protein, human) RN - EC 2.3.2.27 (Ubiquitin-Protein Ligases) RN - EC 2.7.10.1 (Receptor, Macrophage Colony-Stimulating Factor) SB - IM MH - Animals MH - *Apoptosis MH - Cells, Cultured MH - Cyclin-Dependent Kinase Inhibitor p27/*immunology MH - Dendritic Cells/*cytology/immunology/metabolism MH - Gene Expression MH - Humans MH - Interferon-gamma/immunology MH - Interleukin-12/*immunology MH - Mice MH - Mice, Inbred C57BL MH - MicroRNAs/genetics/*immunology MH - Receptor, Macrophage Colony-Stimulating Factor/immunology MH - Suppressor of Cytokine Signaling 1 Protein MH - Suppressor of Cytokine Signaling Proteins/*immunology MH - Ubiquitin-Protein Ligases/*immunology PMC - PMC3087479 EDAT- 2011/03/01 06:00 MHDA- 2011/07/14 06:00 PMCR- 2012/04/21 CRDT- 2011/03/01 06:00 PHST- 2011/03/01 06:00 [entrez] PHST- 2011/03/01 06:00 [pubmed] PHST- 2011/07/14 06:00 [medline] PHST- 2012/04/21 00:00 [pmc-release] AID - S0006-4971(20)45241-3 [pii] AID - 2010/322503 [pii] AID - 10.1182/blood-2010-12-322503 [doi] PST - ppublish SO - Blood. 2011 Apr 21;117(16):4293-303. doi: 10.1182/blood-2010-12-322503. Epub 2011 Feb 25.