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Updated: Apr 27, 2026
In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
The tumor-suppressive microRNA-135b targets c-myc in osteoscarcoma
Zheng Liu1, Guangwu Zhang1, Jian Li1
1Department of Orthopedic Surgery, Peking University Shougang Hospital, Beijing, China.
Abstract:
Osteosarcoma is the most common primary tumor of the bone. It leads to many deaths because of its rapid proliferation and metastasis. Recent studies have shown that microRNAs are important gene regulators that are involved in various cancer-related processes. In this study, we found that miR-135b was down-regulated in both osteoscarcoma patient tumor tissues and osteoscarcoma cell lines in comparison to paired adjacent non-tumor bone tissue. We observed that a lower level of miR-135b was associated with metastasis. The ectopic expression of miR-135b markedly suppressed osteoscarcoma cell proliferation, migration, and invasion. Conversely, the inhibition of miR-135b expression dramatically accelerated cell proliferation, migration, and invasion. The forced expression of miR-135b in osteosarcoma cells resulted in a significant reduction in the protein level of c-Myc and repressed the activity of a luciferase reporter that contained the 3'-untranslated region of the c-Myc mRNA. These effects were abolished by the mutation of the predicted miR-135b-binding site, which indicates that c-Myc may be a miR-135b target gene. Moreover, the ectopic expression of c-Myc partially reversed the inhibition of cell proliferation and invasion that was caused by miR-135b. These data therefore suggest that miR-135b may function as a tumor suppressor to regulate osteosarcoma cell proliferation and invasion through a mechanism that targets the c-Myc oncogene. These findings indicate that miR-135b may play a role in the pathogenesis of osteosarcoma.
Insights
MicroRNA-135b (miR-135b) is downregulated in osteosarcoma, correlating with metastasis. Restoring miR-135b suppresses tumor growth and invasion by targeting the c-Myc oncogene, suggesting its tumor suppressor role.
Area of Science:
- Oncology
- Molecular Biology
- Gene Regulation
Background:
- Osteosarcoma is the most common primary bone tumor, characterized by rapid proliferation and metastasis, leading to high mortality.
- MicroRNAs (miRNAs) are crucial gene regulators implicated in various cancer processes.
- Understanding the role of specific miRNAs in osteosarcoma pathogenesis is vital for developing targeted therapies.
Purpose of the Study:
- To investigate the role of miR-135b in osteosarcoma.
- To determine the relationship between miR-135b expression levels and osteosarcoma progression, including metastasis.
- To elucidate the molecular mechanism by which miR-135b regulates osteosarcoma cell behavior.
Main Methods:
- Quantitative analysis of miR-135b expression in osteosarcoma tissues and cell lines compared to non-tumor controls.
- In vitro experiments involving ectopic expression and inhibition of miR-135b to assess effects on cell proliferation, migration, and invasion.
- Luciferase reporter assays to validate c-Myc as a direct target of miR-135b.
- Western blot analysis to evaluate protein levels of c-Myc.
- Rescue experiments with c-Myc overexpression to confirm its role in miR-135b-mediated effects.
Main Results:
- miR-135b was significantly downregulated in osteosarcoma tissues and cell lines.
- Lower miR-135b levels were associated with increased metastasis.
- Ectopic miR-135b expression suppressed osteosarcoma cell proliferation, migration, and invasion.
- miR-135b directly targets and reduces c-Myc protein levels.
- Overexpression of c-Myc partially reversed the tumor-suppressive effects of miR-135b.
Conclusions:
- miR-135b acts as a tumor suppressor in osteosarcoma.
- The tumor-suppressive function of miR-135b is mediated through the downregulation of the c-Myc oncogene.
- miR-135b holds potential as a therapeutic target for osteosarcoma treatment.
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