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Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
The Effects of MiR-214-3p and Irisin/FNDC5 on the Biological Behavior of Osteosarcoma Cells
Gong Cheng1, Dong Xu2, Kai Chu1
1Department of Orthopedics, Yantaishan Hospital, Yantai, China.
Abstract:
Irisin/fibronectin type III domain-containing protein 5 (FNDC5) has important effects on breast cancer and liver cancer, however, its role in osteosarcoma is poorly understood. This study explored the effects of irisin/FNDC5 in osteosarcoma cells, aiming to provide a direction for treating osteosarcoma. The expression levels of irisin/FNDC5 in serums and tissues of osteosarcoma patients and the expression characteristics of FNDC5 in osteosarcoma cell lines were measured. The effects of irisin, at different concentrations (0, 25, 50, 100, and 200 ng/mL), and FNDC5 on the viability, migration, and invasion of U2OS cells were analyzed. The target gene regulating FNDC5 was predicted, and its effects on irisin/FNDC5 and osteosarcoma cells were further explored. The authors found that irisin/FNDC5 was significantly downregulated in the serums and tissues of osteosarcoma patients, and FNDC5 was also lowly expressed in osteosarcoma cell lines, especially in U2OS cells. Irisin/FNDC5 could not only inhibit the viability of U2OS cell in a concentration- and time-dependent manner but could also suppress cell migration and invasion. Furthermore, miR-214-3p inhibited the expression of irisin/FNDC5, and promoted the migration, invasion, and epithelial/mesenchymal transition (EMT) of U2OS cell through targeting FNDC5. Irisin/FNDC5 could inhibit the viability, migration, invasion, and EMT of osteosarcoma cells, and miR-214-3p could target FNDC5 to release its antitumor effects. Thus, irisin/FNDC5 and miR-214-3p might become a new direction for the treatment of osteosarcoma patients in the future.
Insights
Fibronectin type III domain-containing protein 5 (FNDC5) and miR-214-3p show potential for osteosarcoma treatment. FNDC5 inhibits cancer cell viability, migration, and invasion, while miR-214-3p targets FNDC5 to exert antitumor effects.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- The role of fibronectin type III domain-containing protein 5 (FNDC5) in osteosarcoma remains largely unexplored, despite its known effects in other cancers.
- Understanding FNDC5's function in osteosarcoma is crucial for developing novel therapeutic strategies.
Purpose of the Study:
- To investigate the expression of irisin/FNDC5 in osteosarcoma.
- To determine the effects of irisin/FNDC5 on osteosarcoma cell behavior (viability, migration, invasion).
- To identify regulatory mechanisms involving FNDC5 in osteosarcoma.
Main Methods:
- Quantitative analysis of irisin/FNDC5 expression in patient serums and tissues.
- In vitro experiments assessing the impact of irisin/FNDC5 on U2OS osteosarcoma cell lines.
- Bioinformatic prediction and experimental validation of FNDC5 regulatory elements, including microRNAs.
Main Results:
- Irisin/FNDC5 expression was significantly downregulated in osteosarcoma patient samples and cell lines.
- Irisin/FNDC5 inhibited osteosarcoma cell viability, migration, and invasion in a dose- and time-dependent manner.
- MiR-214-3p was identified as an inhibitor of FNDC5, promoting osteosarcoma cell migration, invasion, and epithelial-mesenchymal transition (EMT).
Conclusions:
- Irisin/FNDC5 exhibits significant antitumor properties against osteosarcoma by suppressing cell viability, migration, invasion, and EMT.
- MiR-214-3p acts as a tumor suppressor in osteosarcoma by targeting FNDC5.
- Both irisin/FNDC5 and miR-214-3p represent promising therapeutic targets for osteosarcoma treatment.
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