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Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells

Osteosarcomas are the most common type of malignant bone tumor. These tumors are characterized by the synthesis of an osteoid matrix. Current treatments are based on surgery and combination chemotherapy. However, for metastatic or recurrent tumors, chemotherapy is generally ineffective, and osteosar...

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Autores principales: Veys, Clément, Jammes, Manon, Rédini, Françoise, Poulain, Laurent, Denoyelle, Christophe, Legendre, Florence, Galera, Philippe
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949568/
https://www.ncbi.nlm.nih.gov/pubmed/35337159
http://dx.doi.org/10.3390/ph15030362
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author Veys, Clément
Jammes, Manon
Rédini, Françoise
Poulain, Laurent
Denoyelle, Christophe
Legendre, Florence
Galera, Philippe
author_facet Veys, Clément
Jammes, Manon
Rédini, Françoise
Poulain, Laurent
Denoyelle, Christophe
Legendre, Florence
Galera, Philippe
author_sort Veys, Clément
collection PubMed
description Osteosarcomas are the most common type of malignant bone tumor. These tumors are characterized by the synthesis of an osteoid matrix. Current treatments are based on surgery and combination chemotherapy. However, for metastatic or recurrent tumors, chemotherapy is generally ineffective, and osteosarcomas are sometimes unresectable. Thus, the use of microRNAs (miRNAs) may represent an attractive alternative for the development of new therapies. Using high-throughput functional screening based on impedancemetry, we previously selected five miRNAs with potential chemosensitizing or antiproliferative effects on chondrosarcoma cells. We validated the tumor-suppressive activity of miR-491-5p and miR-342-5p in three chondrosarcoma cell lines. Here, we carried out individual functional validation of these five miRNAs in three osteosarcoma cell lines used as controls to evaluate their specificity of action on another type of bone sarcoma. The cytotoxic effects of miR-491-5p and miR-342-5p were also confirmed in osteosarcoma cells. Both miRNAs induced apoptosis. They increased Bcl-2 homologous antagonist killer (Bak) protein expression and directly targeted Bcl-2 lymphoma-extra large (Bcl-xL). MiR-342-5p also decreased B-cell lymphoma-2 (Bcl-2) protein expression, and miR-491-5p decreased that of Epidermal Growth Factor Receptor (EGFR). MiR-342-5p and miR-491-5p show tumor-suppressive activity in osteosarcomas. This study also confirms the potential of Bcl-xL as a therapeutic target in osteosarcomas.
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spelling pubmed-89495682022-03-26 Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells Veys, Clément Jammes, Manon Rédini, Françoise Poulain, Laurent Denoyelle, Christophe Legendre, Florence Galera, Philippe Pharmaceuticals (Basel) Article Osteosarcomas are the most common type of malignant bone tumor. These tumors are characterized by the synthesis of an osteoid matrix. Current treatments are based on surgery and combination chemotherapy. However, for metastatic or recurrent tumors, chemotherapy is generally ineffective, and osteosarcomas are sometimes unresectable. Thus, the use of microRNAs (miRNAs) may represent an attractive alternative for the development of new therapies. Using high-throughput functional screening based on impedancemetry, we previously selected five miRNAs with potential chemosensitizing or antiproliferative effects on chondrosarcoma cells. We validated the tumor-suppressive activity of miR-491-5p and miR-342-5p in three chondrosarcoma cell lines. Here, we carried out individual functional validation of these five miRNAs in three osteosarcoma cell lines used as controls to evaluate their specificity of action on another type of bone sarcoma. The cytotoxic effects of miR-491-5p and miR-342-5p were also confirmed in osteosarcoma cells. Both miRNAs induced apoptosis. They increased Bcl-2 homologous antagonist killer (Bak) protein expression and directly targeted Bcl-2 lymphoma-extra large (Bcl-xL). MiR-342-5p also decreased B-cell lymphoma-2 (Bcl-2) protein expression, and miR-491-5p decreased that of Epidermal Growth Factor Receptor (EGFR). MiR-342-5p and miR-491-5p show tumor-suppressive activity in osteosarcomas. This study also confirms the potential of Bcl-xL as a therapeutic target in osteosarcomas. MDPI 2022-03-16 /pmc/articles/PMC8949568/ /pubmed/35337159 http://dx.doi.org/10.3390/ph15030362 Text en © 2022 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 Article
Veys, Clément
Jammes, Manon
Rédini, Françoise
Poulain, Laurent
Denoyelle, Christophe
Legendre, Florence
Galera, Philippe
Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells
title Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells
title_full Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells
title_fullStr Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells
title_full_unstemmed Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells
title_short Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells
title_sort tumor suppressive role of mir-342-5p and mir-491-5p in human osteosarcoma cells
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8949568/
https://www.ncbi.nlm.nih.gov/pubmed/35337159
http://dx.doi.org/10.3390/ph15030362
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