MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells
Chondrosarcomas and osteosarcomas are malignant bone tumors with a poor prognosis when unresectable or metastasized. Moreover, radiotherapy and chemotherapy could be ineffective. MiRNAs represent an alternative therapeutic approach. Based on high-throughput functional screening, we identified four m...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-08-01
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| Series: | Frontiers in Oncology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fonc.2023.1220459/full |
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| author | Clément Veys Flavie Boulouard Flavie Boulouard Abderrahim Benmoussa Abderrahim Benmoussa Manon Jammes Emilie Brotin Emilie Brotin Emilie Brotin Françoise Rédini Laurent Poulain Laurent Poulain Nicolas Gruchy Nicolas Gruchy Christophe Denoyelle Christophe Denoyelle Christophe Denoyelle Florence Legendre Philippe Galera |
| author_facet | Clément Veys Flavie Boulouard Flavie Boulouard Abderrahim Benmoussa Abderrahim Benmoussa Manon Jammes Emilie Brotin Emilie Brotin Emilie Brotin Françoise Rédini Laurent Poulain Laurent Poulain Nicolas Gruchy Nicolas Gruchy Christophe Denoyelle Christophe Denoyelle Christophe Denoyelle Florence Legendre Philippe Galera |
| author_sort | Clément Veys |
| collection | DOAJ |
| description | Chondrosarcomas and osteosarcomas are malignant bone tumors with a poor prognosis when unresectable or metastasized. Moreover, radiotherapy and chemotherapy could be ineffective. MiRNAs represent an alternative therapeutic approach. Based on high-throughput functional screening, we identified four miRNAs with a potential antiproliferative effect on SW1353 chondrosarcoma cells. Individual functional validations were then performed in SW1353 cells, as well as in three osteosarcoma cell lines. The antiproliferative and cytotoxic effects of miRNAs were evaluated in comparison with a positive control, miR-342-5p. The cytotoxic effect of four selected miRNAs was not confirmed on SW1353 cells, but we unambiguously revealed that miR-4270 had a potent cytotoxic effect on HOS and MG-63 osteosarcoma cell lines, but not on SaOS-2 cell line. Furthermore, like miR-342-5p, miR-4270 induced apoptosis in these two cell lines. In addition, we provided the first report of Bcl-xL as a direct target of miR-4270. MiR-4270 also decreased the expression of the anti-apoptotic protein Mcl-1, and increased the expression of the pro-apoptotic protein Bak. Our findings demonstrated that miR-4270 has tumor suppressive activity in osteosarcoma cells, particularly through Bcl-xL downregulation. |
| first_indexed | 2024-03-12T11:42:57Z |
| format | Article |
| id | doaj.art-ca6a80213c7749da80be7ec384cce913 |
| institution | Directory Open Access Journal |
| issn | 2234-943X |
| language | English |
| last_indexed | 2024-03-12T11:42:57Z |
| publishDate | 2023-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Oncology |
| spelling | doaj.art-ca6a80213c7749da80be7ec384cce9132023-08-31T12:54:22ZengFrontiers Media S.A.Frontiers in Oncology2234-943X2023-08-011310.3389/fonc.2023.12204591220459MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cellsClément Veys0Flavie Boulouard1Flavie Boulouard2Abderrahim Benmoussa3Abderrahim Benmoussa4Manon Jammes5Emilie Brotin6Emilie Brotin7Emilie Brotin8Françoise Rédini9Laurent Poulain10Laurent Poulain11Nicolas Gruchy12Nicolas Gruchy13Christophe Denoyelle14Christophe Denoyelle15Christophe Denoyelle16Florence Legendre17Philippe Galera18Normandie Univ., UNICAEN, BIOTARGEN, Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, Caen, FranceDepartment of Genetics, Normandy Center for Genomic and Personalized Medicine, Caen University Hospital, Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, Caen, FranceResearch Center of the UHC Sainte-Justine and Department of Nutrition, Université de Montréal, Montréal, QC, CanadaNormandie Univ., UNICAEN, BIOTARGEN, Caen, FranceNormandie Univ., UNICAEN, Federative Structure Normandie Oncology, US Platon, ImpedanCELL Platform, Caen, FranceNormandie Univ., UNICAEN, INSERM U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, FranceUNICANCER, Comprehensive Cancer Center F. Baclesse, Caen, FranceUMR 1238 Phy-Os “Bone Sarcomas and Remodeling of Calcified Tissues”, INSERM, Nantes University, Nantes, FranceNormandie Univ., UNICAEN, INSERM U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, FranceUNICANCER, Comprehensive Cancer Center F. Baclesse, Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, Caen, FranceDepartment of Genetics, Normandy Center for Genomic and Personalized Medicine, Caen University Hospital, Caen, FranceNormandie Univ., UNICAEN, Federative Structure Normandie Oncology, US Platon, ImpedanCELL Platform, Caen, FranceNormandie Univ., UNICAEN, INSERM U1086 ANTICIPE, Biology and Innovative Therapeutics for Ovarian Cancer (BioTICLA), Caen, FranceUNICANCER, Comprehensive Cancer Center F. Baclesse, Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, Caen, FranceNormandie Univ., UNICAEN, BIOTARGEN, Caen, FranceChondrosarcomas and osteosarcomas are malignant bone tumors with a poor prognosis when unresectable or metastasized. Moreover, radiotherapy and chemotherapy could be ineffective. MiRNAs represent an alternative therapeutic approach. Based on high-throughput functional screening, we identified four miRNAs with a potential antiproliferative effect on SW1353 chondrosarcoma cells. Individual functional validations were then performed in SW1353 cells, as well as in three osteosarcoma cell lines. The antiproliferative and cytotoxic effects of miRNAs were evaluated in comparison with a positive control, miR-342-5p. The cytotoxic effect of four selected miRNAs was not confirmed on SW1353 cells, but we unambiguously revealed that miR-4270 had a potent cytotoxic effect on HOS and MG-63 osteosarcoma cell lines, but not on SaOS-2 cell line. Furthermore, like miR-342-5p, miR-4270 induced apoptosis in these two cell lines. In addition, we provided the first report of Bcl-xL as a direct target of miR-4270. MiR-4270 also decreased the expression of the anti-apoptotic protein Mcl-1, and increased the expression of the pro-apoptotic protein Bak. Our findings demonstrated that miR-4270 has tumor suppressive activity in osteosarcoma cells, particularly through Bcl-xL downregulation.https://www.frontiersin.org/articles/10.3389/fonc.2023.1220459/fullosteosarcomachondrosarcomamiR-4270miR-342-5papoptosisBcl-XL |
| spellingShingle | Clément Veys Flavie Boulouard Flavie Boulouard Abderrahim Benmoussa Abderrahim Benmoussa Manon Jammes Emilie Brotin Emilie Brotin Emilie Brotin Françoise Rédini Laurent Poulain Laurent Poulain Nicolas Gruchy Nicolas Gruchy Christophe Denoyelle Christophe Denoyelle Christophe Denoyelle Florence Legendre Philippe Galera MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells Frontiers in Oncology osteosarcoma chondrosarcoma miR-4270 miR-342-5p apoptosis Bcl-XL |
| title | MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells |
| title_full | MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells |
| title_fullStr | MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells |
| title_full_unstemmed | MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells |
| title_short | MiR-4270 acts as a tumor suppressor by directly targeting Bcl-xL in human osteosarcoma cells |
| title_sort | mir 4270 acts as a tumor suppressor by directly targeting bcl xl in human osteosarcoma cells |
| topic | osteosarcoma chondrosarcoma miR-4270 miR-342-5p apoptosis Bcl-XL |
| url | https://www.frontiersin.org/articles/10.3389/fonc.2023.1220459/full |
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