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Updated: Mar 8, 2026
A Preclinical Mouse Model of Osteosarcoma to Define the Extracellular Vesicle-mediated Communication Between Tumor and Mesenchymal Stem Cells
Published on: May 6, 2018
miR-574-3p acts as a tumor promoter in osteosarcoma by targeting SMAD4 signaling pathway
Haidong Xu1, Xiaozhou Liu1, Juan Zhou1
1Department of Orthopedics of Jinling Hospital, Nanjing University, School of Medicine, Nanjing, Jiangsu 210002, P.R. China.
Abstract:
Human osteosarcoma is the most common primary bone malignancy sarcoma that affects primarily children and people <20 years old. In the present study, it was demonstrated that miR-574-3p was downregulated in human osteosarcoma U2OS, SAOS and MG63 cells lines as well as in osteosarcoma tissue compared with the normal tissues. Downregulation of miR-574-3p by antisense miR-574-3p, inhibited cell growth and induced cell apoptosis. Overexpression of miR-574-3p by transfection with miR-574-3p mimics promoted the growth of U2OS cells. The present study then identified mothers against decapentaplegic homolog 4 (SMAD4) as a target of miR-574-3p and SMAD4 was suppressed in miR-574-3p transfected cells. Overexpression of SMAD4 could rescue the promoting effects of miR-574-3p on cancer cell growth. In conclusion, miR-574-3p exerts tumor-promoting roles by targeting the tumor-suppressing gene SMAD4 and its downstream signaling in human osteosarcoma, which provides a novel target for the treatment.
Insights
MicroRNA-574-3p (miR-574-3p) is downregulated in human osteosarcoma, promoting cancer cell growth by targeting SMAD4. Restoring miR-574-3p may offer a novel therapeutic strategy for osteosarcoma treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Human osteosarcoma is a prevalent bone cancer primarily affecting young individuals.
- Understanding the molecular mechanisms driving osteosarcoma progression is crucial for developing effective treatments.
Purpose of the Study:
- To investigate the role of microRNA-574-3p (miR-574-3p) in human osteosarcoma.
- To identify the molecular targets and signaling pathways regulated by miR-574-3p in osteosarcoma.
Main Methods:
- Quantitative real-time PCR to assess miR-574-3p expression in osteosarcoma cell lines and tissues.
- Cell viability assays and apoptosis assays to evaluate the functional role of miR-574-3p.
- Western blotting and luciferase reporter assays to identify and validate SMAD4 as a direct target of miR-574-3p.
Main Results:
- miR-574-3p was significantly downregulated in human osteosarcoma cells and tissues compared to normal controls.
- Downregulation of miR-574-3p inhibited cell growth and induced apoptosis, while its overexpression promoted cell proliferation.
- Mothers against decapentaplegic homolog 4 (SMAD4) was identified as a direct target of miR-574-3p, and its expression was inversely correlated with miR-574-3p levels.
- Overexpression of SMAD4 partially rescued the effects of miR-574-3p on osteosarcoma cell growth.
Conclusions:
- miR-574-3p functions as a tumor suppressor in human osteosarcoma by targeting SMAD4.
- The miR-574-3p/SMAD4 axis represents a potential therapeutic target for osteosarcoma treatment.
