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Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner
The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell...
Autores principales: | , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095495/ https://www.ncbi.nlm.nih.gov/pubmed/37047835 http://dx.doi.org/10.3390/ijms24076862 |
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author | Vulpis, Elisabetta Cuollo, Lorenzo Borrelli, Cristiana Antonangeli, Fabrizio Masuelli, Laura Cippitelli, Marco Fionda, Cinzia Caracciolo, Giulio Petrucci, Maria Teresa Santoni, Angela Zingoni, Alessandra Soriani, Alessandra |
author_facet | Vulpis, Elisabetta Cuollo, Lorenzo Borrelli, Cristiana Antonangeli, Fabrizio Masuelli, Laura Cippitelli, Marco Fionda, Cinzia Caracciolo, Giulio Petrucci, Maria Teresa Santoni, Angela Zingoni, Alessandra Soriani, Alessandra |
author_sort | Vulpis, Elisabetta |
collection | PubMed |
description | The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. Senescent cells undergo morphological change and context-dependent functional diversification, acquiring the ability to secrete a vast pool of molecules termed the senescence-associated secretory phenotype (SASP), which affects neighboring cells. Recently, exosomes have been recognized as SASP factors, contributing to modulating a variety of cell functions. In particular, evidence suggests a key role for exosomal microRNAs in influencing many hallmarks of cancer. Herein, we demonstrate that doxorubicin treatment of MM cells leads to the enrichment of miR-433 into exosomes, which in turn induces bystander senescence. Our analysis reveals that the establishment of the senescent phenotype on neighboring MM cells is p53- and p21-independent and is related to CDK-6 down-regulation. Notably, miR-433-dependent senescence does not induce the up-regulation of activating ligands on MM cells. Altogether, our findings highlight the possibility of miR-433-enriched exosomes to reinforce doxorubicin-mediated cellular senescence. |
format | Online Article Text |
id | pubmed-10095495 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100954952023-04-13 Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner Vulpis, Elisabetta Cuollo, Lorenzo Borrelli, Cristiana Antonangeli, Fabrizio Masuelli, Laura Cippitelli, Marco Fionda, Cinzia Caracciolo, Giulio Petrucci, Maria Teresa Santoni, Angela Zingoni, Alessandra Soriani, Alessandra Int J Mol Sci Brief Report The success of senescence-based anticancer therapies relies on their anti-proliferative power and on their ability to trigger anti-tumor immune responses. Indeed, genotoxic drug-induced senescence increases the expression of NK cell-activating ligands on multiple myeloma (MM) cells, boosting NK cell recognition and effector functions. Senescent cells undergo morphological change and context-dependent functional diversification, acquiring the ability to secrete a vast pool of molecules termed the senescence-associated secretory phenotype (SASP), which affects neighboring cells. Recently, exosomes have been recognized as SASP factors, contributing to modulating a variety of cell functions. In particular, evidence suggests a key role for exosomal microRNAs in influencing many hallmarks of cancer. Herein, we demonstrate that doxorubicin treatment of MM cells leads to the enrichment of miR-433 into exosomes, which in turn induces bystander senescence. Our analysis reveals that the establishment of the senescent phenotype on neighboring MM cells is p53- and p21-independent and is related to CDK-6 down-regulation. Notably, miR-433-dependent senescence does not induce the up-regulation of activating ligands on MM cells. Altogether, our findings highlight the possibility of miR-433-enriched exosomes to reinforce doxorubicin-mediated cellular senescence. MDPI 2023-04-06 /pmc/articles/PMC10095495/ /pubmed/37047835 http://dx.doi.org/10.3390/ijms24076862 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Brief Report Vulpis, Elisabetta Cuollo, Lorenzo Borrelli, Cristiana Antonangeli, Fabrizio Masuelli, Laura Cippitelli, Marco Fionda, Cinzia Caracciolo, Giulio Petrucci, Maria Teresa Santoni, Angela Zingoni, Alessandra Soriani, Alessandra Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner |
title | Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner |
title_full | Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner |
title_fullStr | Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner |
title_full_unstemmed | Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner |
title_short | Doxorubicin–Mediated miR–433 Expression on Exosomes Promotes Bystander Senescence in Multiple Myeloma Cells in a DDR–Independent Manner |
title_sort | doxorubicin–mediated mir–433 expression on exosomes promotes bystander senescence in multiple myeloma cells in a ddr–independent manner |
topic | Brief Report |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10095495/ https://www.ncbi.nlm.nih.gov/pubmed/37047835 http://dx.doi.org/10.3390/ijms24076862 |
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