miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma
- Autori: Rossi, M.; Altomare, E.; Botta, C.; Gallo Cantafio, M.E.; Sarvide, S.; Caracciolo, D.; Riillo, C.; Gaspari, M.; Taverna, D.; Conforti, F.; Critelli, P.; Bertucci, B.; Iannone, M.; Polera, N.; Scumaci, D.; Arbitrio, M.; Amodio, N.; Di Martino, M.T.; Paiva, B.; Tagliaferri, P.; Tassone, P.
- Anno di pubblicazione: 2021
- Tipologia: Articolo in rivista
- OA Link: http://hdl.handle.net/10447/513411
Abstract
Multiple myeloma (MM) is tightly dependent on inflammatory bone marrow microenvironment. IL-17 producing CD4+ T cells (Th17) sustain MM cells growth and osteoclasts-dependent bone damage. In turn, Th17 differentiation relies on inflammatory stimuli. Here, we investigated the role of miR-21 in Th17-mediated MM tumor growth and bone disease. We found that early inhibition of miR-21 in naive T cells (miR-21i-T cells) impaired Th17 differentiation in vitro and abrogated Th17-mediated MM cell proliferation and osteoclasts activity. We validated these findings in NOD/SCID-g-NULL mice, intratibially injected with miR-21i-T cells and MM cells. A Pairwise RNAseq and proteome/phosphoproteome analysis in Th17 cells demonstrated that miR-21 inhibition led to upregulation of STAT-1/-5a-5b, STAT-3 impairment and redirection of Th17 to Th1/Th2 like activated/polarized cells. Our findings disclose the role of miR-21 in pathogenic Th17 activity and open the avenue to the design of miR-21-targeting strategies to counteract microenvironment dependence of MM growth and bone disease.