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Updated: Oct 4, 2025
Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
MicroRNA-494 represses osteosarcoma development by modulating ASK-1 related apoptosis complexes
1Guizhou Provincial People's Hospital, Guiyang, China.
Background:
MicroRNA (miR)-494 had been proven to be involved in tumor pathogenesis, while studies on miR-494 and osteosarcoma (OS) are still limited. In the current study, we aimed to explore the expression pattern and the roles of miR-494 in the development of OS.
Methods:
Mouse models and osteoblastic cells were used to investigate the functions of miR-494. A case-control study including 87 OS patients and 100 controls was also conducted to investigate the prognostic value of miR-494.
Results:
Animal researches and human studies showed that miR-494 expression level in OS tissue (OST) was down-regulated compared to paracancerous tissue (PT), and had a significant positive association with its level in serum (P<0.05). Gain of miR-494 function suppressed OS tumor growth and promoted apoptosis of OS cells, while loss of miR-494 inhibited apoptosis and promoted invasion of osteoblastic cells. MiR-494 expressions in both OST and serum were correlated with the T stage, lymph node metastasis and distant metastasis of OS (P<0.05). Results of survival analysis showed that compared to patients with high miR-494 level, the overall survival rate in 24 months was significantly lower in the low miR-494 group (P<0.05). In vitro study revealed that miR-494 interacted with apoptosis signal regulating kinase 1 (ASK-1)/serine-threonine kinase receptor-associated protein (STRAP)/14-3-3 complex to promote the activation of tumor necrosis factor-α (TNF-α)/ASK-1-mediated apoptosis.
Conclusions:
These results revealed that miR-494 functioned as a tumor suppressor and improved the prognosis of OS via modulating apoptosis complexes.
Insights
MicroRNA-494 (miR-494) acts as a tumor suppressor in osteosarcoma (OS). Lower miR-494 levels correlate with poorer prognosis and increased metastasis, suggesting its potential as a therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- MicroRNA-494 (miR-494) involvement in tumor pathogenesis is known, but its role in osteosarcoma (OS) requires further investigation.
- Limited studies exist on miR-494's specific functions and expression patterns in OS development.
Purpose of the Study:
- To elucidate the expression profile of miR-494 in osteosarcoma.
- To investigate the functional roles of miR-494 in OS progression and development.
- To assess the prognostic significance of miR-494 in OS patients.
Main Methods:
- Utilized mouse models and osteoblastic cell lines to study miR-494 functions.
- Conducted a case-control study with 87 OS patients and 100 controls.
- Analyzed miR-494 expression in tumor and serum samples, correlating with clinical parameters and survival outcomes.
Main Results:
- miR-494 was significantly down-regulated in OS tissues and serum compared to controls, with levels positively associated between tissue and serum.
- Overexpression of miR-494 suppressed OS tumor growth and induced apoptosis, while its depletion promoted cell invasion.
- Low miR-494 expression correlated with advanced T stage, lymph node metastasis, and distant metastasis, predicting poorer overall survival.
- miR-494 modulates the ASK-1/STRAP/14-3-3 complex to promote TNF-α/ASK-1-mediated apoptosis.
Conclusions:
- miR-494 functions as a tumor suppressor in osteosarcoma.
- miR-494 significantly improves the prognosis of OS patients by regulating apoptosis.
- miR-494 represents a potential biomarker and therapeutic target for osteosarcoma.
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