Related Experiment Video
Updated: Nov 3, 2025
Tumorsphere Derivation and Treatment from Primary Tumor Cells Isolated from Mouse Rhabdomyosarcomas
Published on: September 13, 2019
Tumor Suppressive Role of miR-342-5p in Human Chondrosarcoma Cells and 3D Organoids
Clément Veys1, Abderrahim Benmoussa1,2, Romain Contentin1
1Normandie Univ, UNICAEN, BIOTARGEN, 14000 Caen, France.
Abstract:
Chondrosarcomas are malignant bone tumors. Their abundant cartilage-like extracellular matrix and their hypoxic microenvironment contribute to their resistance to chemotherapy and radiotherapy, and no effective therapy is currently available. MicroRNAs (miRNAs) may be an interesting alternative in the development of therapeutic options. Here, for the first time in chondrosarcoma cells, we carried out high-throughput functional screening using impedancemetry, and identified five miRNAs with potential antiproliferative or chemosensitive effects on SW1353 chondrosarcoma cells. The cytotoxic effects of miR-342-5p and miR-491-5p were confirmed on three chondrosarcoma cell lines, using functional validation under normoxia and hypoxia. Both miRNAs induced apoptosis and miR-342-5p also induced autophagy. Western blots and luciferase reporter assays identified for the first time Bcl-2 as a direct target of miR-342-5p, and also Bcl-xL as a direct target of both miR-342-5p and miR-491-5p in chondrosarcoma cells. MiR-491-5p also inhibited EGFR expression. Finally, only miR-342-5p induced cell death on a relevant 3D chondrosarcoma organoid model under hypoxia that mimics the in vivo microenvironment. Altogether, our results revealed the tumor suppressive activity of miR-342-5p, and to a lesser extent of miR-491-5p, on chondrosarcoma lines. Through this study, we also confirmed the potential of Bcl-2 family members as therapeutic targets in chondrosarcomas.
Insights
MicroRNAs (miRNAs) show promise for treating chondrosarcoma, a bone cancer resistant to current therapies. miR-342-5p and miR-491-5p exhibit tumor-suppressive activity by inducing apoptosis and targeting key proteins like Bcl-2.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Chondrosarcomas are malignant bone tumors with poor therapeutic outcomes due to their matrix and hypoxic microenvironment.
- Current treatments for chondrosarcoma lack efficacy, necessitating novel therapeutic strategies.
Purpose of the Study:
- To identify microRNAs (miRNAs) with antiproliferative or chemosensitive effects in chondrosarcoma cells.
- To investigate the therapeutic potential of specific miRNAs in chondrosarcoma, including their mechanisms of action and efficacy in a 3D model.
Main Methods:
- High-throughput functional screening using impedancemetry to identify potential therapeutic miRNAs.
- Cytotoxicity assays, apoptosis and autophagy induction analysis, Western blots, and luciferase reporter assays to validate miRNA effects and targets.
- Evaluation of miRNA efficacy in a 3D chondrosarcoma organoid model under hypoxic conditions.
Main Results:
- Five miRNAs with potential antiproliferative or chemosensitive effects were identified in SW1353 chondrosarcoma cells.
- miR-342-5p and miR-491-5p demonstrated cytotoxic effects, inducing apoptosis, with miR-342-5p also inducing autophagy.
- Bcl-2 and Bcl-xL were identified as direct targets of miR-342-5p, and Bcl-xL as a target of miR-491-5p. EGFR was also inhibited by miR-491-5p.
- miR-342-5p showed significant cell death induction in a 3D hypoxic chondrosarcoma model.
Conclusions:
- miR-342-5p and miR-491-5p exhibit tumor-suppressive properties in chondrosarcoma cell lines.
- Bcl-2 family members represent potential therapeutic targets for chondrosarcoma treatment.
- miR-342-5p holds significant therapeutic potential for chondrosarcoma, particularly in the hypoxic tumor microenvironment.
Related Concept Videos
01:12Loss of Tumor Suppressor Gene Functions
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
02:17The Tumor Microenvironment