PMID- 29158557
OWN - NLM
STAT- MEDLINE
DCOM- 20190219
LR  - 20210614
IS  - 1476-5551 (Electronic)
IS  - 0887-6924 (Print)
IS  - 0887-6924 (Linking)
VI  - 32
IP  - 4
DP  - 2018 Apr
TI  - MiR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple 
      myeloma-educated dendritic cells.
PG  - 1003-1015
LID - 10.1038/leu.2017.336 [doi]
AB  - Dendritic cells (DCs) have a key role in regulating tumor immunity, tumor cell 
      growth and drug resistance. We hypothesized that multiple myeloma (MM) cells 
      might recruit and reprogram DCs to a tumor-permissive phenotype by changes within 
      their microRNA (miRNA) network. By analyzing six different miRNA-profiling data 
      sets, miR-29b was identified as the only miRNA upregulated in normal mature DCs 
      and significantly downregulated in tumor-associated DCs. This finding was 
      validated in primary DCs co-cultured in vitro with MM cell lines and in primary 
      bone marrow DCs from MM patients. In DCs co-cultured with MM cells, enforced 
      expression of miR-29b counteracted pro-inflammatory pathways, including signal 
      transducer and activator of transcription 3 and nuclear factor-kappaB, and 
      cytokine/chemokine signaling networks, which correlated with patients' adverse 
      prognosis and development of bone disease. Moreover, miR-29b downregulated 
      interleukin-23 in vitro and in the SCID-synth-hu in vivo model, and antagonized a 
      Th17 inflammatory response. All together, these effects translated into strong 
      anti-proliferative activity and reduction of genomic instability of MM cells. Our 
      study demonstrates that MM reprograms the DCs functional phenotype by 
      downregulating miR-29b whose reconstitution impairs DCs ability to sustain MM 
      cell growth and survival. These results underscore miR-29b as an innovative and 
      attractive candidate for miRNA-based immune therapy of MM.
FAU - Botta, C
AU  - Botta C
AUID- ORCID: 0000-0002-1522-4504
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Cuce, M
AU  - Cuce M
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Pitari, M R
AU  - Pitari MR
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Caracciolo, D
AU  - Caracciolo D
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Gulla, A
AU  - Gulla A
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Morelli, E
AU  - Morelli E
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Riillo, C
AU  - Riillo C
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Biamonte, L
AU  - Biamonte L
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Gallo Cantafio, M E
AU  - Gallo Cantafio ME
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Prabhala, R
AU  - Prabhala R
AD  - Veterans Administration Boston Healthcare System, West Roxbury, MA, USA.
FAU - Mignogna, C
AU  - Mignogna C
AUID- ORCID: 0000-0001-5576-4946
AD  - Department of Health Science, Magna Graecia University, Catanzaro, Italy.
FAU - Di Vito, A
AU  - Di Vito A
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Altomare, E
AU  - Altomare E
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Amodio, N
AU  - Amodio N
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Di Martino, M T
AU  - Di Martino MT
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Correale, P
AU  - Correale P
AD  - Department of Medical Oncology, 'Bianchi-Melacrino-Morelli' Hospital, Reggio 
      Calabria, Italy.
FAU - Rossi, M
AU  - Rossi M
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Giordano, A
AU  - Giordano A
AD  - Department of Human Pathology and Oncology, University of Siena, Siena, Italy.
AD  - Department of Biology, Center for Biotechnology, Sbarro Institute for Cancer 
      Research and Molecular Medicine, College of Science and Technology, Temple 
      University, Philadelphia, PA, USA.
FAU - Munshi, N C
AU  - Munshi NC
AD  - Veterans Administration Boston Healthcare System, West Roxbury, MA, USA.
AD  - Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical 
      School, Boston, MA, USA.
FAU - Tagliaferri, P
AU  - Tagliaferri P
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
FAU - Tassone, P
AU  - Tassone P
AD  - Department of Experimental and Clinical Medicine, Magna Graecia University, 
      Catanzaro, Italy.
AD  - Department of Biology, Center for Biotechnology, Sbarro Institute for Cancer 
      Research and Molecular Medicine, College of Science and Technology, Temple 
      University, Philadelphia, PA, USA.
LA  - eng
GR  - P01 CA155258/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20171121
PL  - England
TA  - Leukemia
JT  - Leukemia
JID - 8704895
RN  - 0 (MIRN29a microRNA, human)
RN  - 0 (MicroRNAs)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT3 Transcription Factor)
SB  - IM
MH  - Animals
MH  - Bone Marrow/pathology
MH  - Cell Line, Tumor
MH  - Cell Proliferation/genetics
MH  - Dendritic Cells/*pathology
MH  - Down-Regulation/genetics
MH  - Female
MH  - Gene Expression Regulation, Neoplastic/genetics
MH  - Humans
MH  - Inflammation/*genetics
MH  - Mice
MH  - Mice, SCID
MH  - MicroRNAs/*genetics
MH  - Multiple Myeloma/*genetics/*pathology
MH  - NF-kappa B/genetics
MH  - STAT3 Transcription Factor/genetics
MH  - Up-Regulation/genetics
PMC - PMC5886056
COIS- The authors declare no conflict of interest.
EDAT- 2017/11/22 06:00
MHDA- 2019/03/21 06:00
PMCR- 2018/04/05
CRDT- 2017/11/22 06:00
PHST- 2017/08/03 00:00 [received]
PHST- 2017/10/05 00:00 [revised]
PHST- 2017/11/10 00:00 [accepted]
PHST- 2017/11/22 06:00 [pubmed]
PHST- 2019/03/21 06:00 [medline]
PHST- 2017/11/22 06:00 [entrez]
PHST- 2018/04/05 00:00 [pmc-release]
AID - leu2017336 [pii]
AID - 10.1038/leu.2017.336 [doi]
PST - ppublish
SO  - Leukemia. 2018 Apr;32(4):1003-1015. doi: 10.1038/leu.2017.336. Epub 2017 Nov 21.