MIR-29b antagonizes the pro-inflammatory tumor-promoting activity of multiple myeloma-educated dendritic cells
Genre
Journal ArticleDate
2018-04-01Author
Botta, CCucè, M
Pitari, MR
Caracciolo, D
Gullà, A
Morelli, E
Riillo, C
Biamonte, L
Gallo Cantafio, ME
Prabhala, R
Mignogna, C
DI Vito, A
Altomare, E
Amodio, N
DI Martino, MT
Correale, P
Rossi, M
Giordano, A
Munshi, NC
Tagliaferri, P
Tassone, P
Subject
AnimalsBone Marrow
Cell Line, Tumor
Cell Proliferation
Dendritic Cells
Down-Regulation
Female
Gene Expression Regulation, Neoplastic
Humans
Inflammation
Mice
Mice, SCID
MicroRNAs
Multiple Myeloma
NF-kappa B
STAT3 Transcription Factor
Up-Regulation
Permanent link to this record
http://hdl.handle.net/20.500.12613/4848
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10.1038/leu.2017.336Abstract
© 2018 Macmillan Publishers Limited, part of Springer Nature. All rights reserved. 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-κ B, 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.Citation to related work
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http://dx.doi.org/10.34944/dspace/4830