Detalle Publicación

miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma

Autores: Rossi, M. (Autor de correspondencia); Altomare, E.; Botta, C. ; Cantafio, M. E. G.; Sarvide Plano, Sarai; 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, Bruno; Tagliaferri, P.; Tassone, P.
Título de la revista: LEUKEMIA
ISSN: 0887-6924
Volumen: 35
Número: 3
Páginas: 823 - 834
Fecha de publicación: 2021
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.