miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma
| العنوان: | miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma |
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| المؤلفون: | Marco Rossi, Paola Critelli, Caterina Riillo, Nicola Amodio, Bernardo Bertucci, Cirino Botta, Francesco Conforti, Domenica Scumaci, Bruno Paiva, Sarai Sarvide, Marco Gaspari, Pierosandro Tagliaferri, Maria Eugenia Gallo Cantafio, Michelangelo Iannone, Pierfrancesco Tassone, Emanuela Altomare, Maria Teresa Di Martino, Daniele Caracciolo, Nicoletta Polerà, Mariamena Arbitrio, Domenico Taverna |
| المساهمون: | 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. |
| المصدر: | Leukemia (Basingstoke, Online) (2020). doi:10.1038/s41375-020-0947-1 info:cnr-pdr/source/autori:Marco Rossi; Emanuela Altomare; Cirino Botta; Maria Eugenia Gallo Cantafio; Sarai Sarvide; Daniele Caracciolo; Caterina Riillo; Marco Gaspari; Domenico Taverna; Francesco Conforti; Paola Critelli; Bernardo Bertucci; Michelangelo Iannone; Nicoletta Polerà; Domenica Scumaci; Mariamena Arbitrio; Nicola Amodio; Maria Teresa Di Martino; Bruno Paiva; Pierosandro Tagliaferri; Pierfrancesco Tassone;/titolo:miR-21 antagonism abrogates Th17 tumor promoting functions in multiple myeloma/doi:10.1038%2Fs41375-020-0947-1/rivista:Leukemia (Basingstoke, Online)/anno:2020/pagina_da:/pagina_a:/intervallo_pagine:/volume |
| بيانات النشر: | Springer Nature, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, Cancer Research, Bone disease, Apoptosis, Bone Neoplasms, Nod, Mice, SCID, Bone Neoplasm, T-Lymphocytes, Regulatory, Th17 Cell, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, gammopathies, Mice, Inbred NOD, medicine, Tumor Cells, Cultured, Tumor Microenvironment, Biomarkers, Tumor, Animals, Humans, Multiple myeloma, Cell Proliferation, Chemistry, Cell growth, Animal, Apoptosi, Hematology, medicine.disease, Prognosis, Xenograft Model Antitumor Assays, In vitro, Gene Expression Regulation, Neoplastic, MicroRNAs, 030104 developmental biology, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Case-Control Studies, Cancer research, Th17 Cells, Bone marrow, Antagonism, Case-Control Studie, Multiple Myeloma |
| الوصف: | 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. |
| اللغة: | English |
| DOI: | 10.1038/s41375-020-0947-1 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::67f11d926913570c25e59a3a64233acd http://hdl.handle.net/10447/513411 |
| Rights: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....67f11d926913570c25e59a3a64233acd |
| قاعدة البيانات: | OpenAIRE |
| DOI: | 10.1038/s41375-020-0947-1 |
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