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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MDPI AG
2022-03-01
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| Online Access: | https://www.mdpi.com/1424-8247/15/3/362 |
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| author | Clément Veys Manon Jammes Françoise Rédini Laurent Poulain Christophe Denoyelle Florence Legendre Philippe Galera |
| author_facet | Clément Veys Manon Jammes Françoise Rédini Laurent Poulain Christophe Denoyelle Florence Legendre Philippe Galera |
| author_sort | Clément Veys |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-09T13:01:12Z |
| format | Article |
| id | doaj.art-d1d827e8820942d1898f94ac37aced44 |
| institution | Directory Open Access Journal |
| issn | 1424-8247 |
| language | English |
| last_indexed | 2024-03-09T13:01:12Z |
| publishDate | 2022-03-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceuticals |
| spelling | doaj.art-d1d827e8820942d1898f94ac37aced442023-11-30T21:55:02ZengMDPI AGPharmaceuticals1424-82472022-03-0115336210.3390/ph15030362Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma CellsClément Veys0Manon Jammes1Françoise Rédini2Laurent Poulain3Christophe Denoyelle4Florence Legendre5Philippe Galera6Normandie Univ., UNICAEN, BIOTARGEN, 14000 Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, 14000 Caen, FranceUMR 1238 Phy-Os “Bone Sarcomas and Remodeling of Calcified Tissues”, INSERM, Nantes University, 44035 Nantes, FranceNormandie Univ., UNICAEN, INSERM U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), 14000 Caen, FranceNormandie Univ., UNICAEN, INSERM U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), 14000 Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, 14000 Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, 14000 Caen, FranceOsteosarcomas 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.https://www.mdpi.com/1424-8247/15/3/362osteosarcomaBcl-2/Bcl-xLmiR-491-5pmiR-342-5pBakapoptosis |
| spellingShingle | Clément Veys Manon Jammes Françoise Rédini Laurent Poulain Christophe Denoyelle Florence Legendre Philippe Galera Tumor Suppressive Role of miR-342-5p and miR-491-5p in Human Osteosarcoma Cells Pharmaceuticals osteosarcoma Bcl-2/Bcl-xL miR-491-5p miR-342-5p Bak apoptosis |
| 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 | osteosarcoma Bcl-2/Bcl-xL miR-491-5p miR-342-5p Bak apoptosis |
| url | https://www.mdpi.com/1424-8247/15/3/362 |
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