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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...
Autores principales: | , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
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MDPI
2022
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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. |
format | Online Article Text |
id | pubmed-8949568 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
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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