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In Vivo Inhibition of MicroRNA to Decrease Tumor Growth in Mice
Published on: August 23, 2019
MicroRNA-139 inhibits the proliferation and migration of osteosarcoma cells via targeting forkhead-box P2
Chunan Zhong1, Jijun Liu1, Yuzhe Zhang1
1Department of Orthopedics, Henan Province People's Hospital, Zhengzhou 450003, China.
Aims:
Osteosarcoma (OS) is the most common primary bone malignancy that affects adolescents. Although great attention has been paid to the diagnosis of and therapy for OS, the 5-year survival rate of patients with this disease remains poor. MicroRNAs are small non-coding RNAs involved in pathogenesis and progression of human malignancies. MiR-139 has been implicated in several human cancers. However, the role played by miR-139 in pathogenesis of human OS has remained largely unknown.
Main Methods:
Realtime PCR was used to detect the expression of miR-139. CCK-8, BrdU-ELISA and ApoTox-Glo™ Triplex assay was employed to detect the proliferation and apoptosis of osteosarcoma cells. Realtime PCR, Western Blotting and luciferase report assays were conducted for the target genes analysis.
Key Findings:
The expression of miR-139 was reduced while the expression of forkhead-box P2 (FOXP2) was induced in both OS tissue and cell lines. The reduced level of miR-139 was correlated with tumor size, clinical stage and distant metastasis. Overexpression of miR-139 inhibited the expression of FOXP2, which suppressed cell growth, but induced apoptosis. Further, we confirmed that FOXP2 was a direct target of miR-139 by luciferase reporter assay. Knockdown of FOXP2 resulted in reduced levels of cell proliferation, but increased levels of apoptosis in vitro.
Significance:
These findings suggest that miR-139 plays a suppressive role in the regulation of OS cell proliferation and migration via directly targeting FOXP2, which might be a potential clinical diagnostic or predictive biomarker for human OS.
Insights
MicroRNA-139 (miR-139) is downregulated in osteosarcoma (OS) and suppresses tumor growth by targeting FOXP2. This suggests miR-139 could be a biomarker for OS.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is a primary bone cancer in adolescents with poor survival rates.
- MicroRNAs (miRNAs) are key regulators in cancer development, but miR-139's role in OS is unclear.
Purpose of the Study:
- Investigate the role of miR-139 in osteosarcoma pathogenesis.
- Identify miR-139's molecular targets and their function in OS cells.
Main Methods:
- Real-time PCR to quantify miR-139 and FOXP2 expression.
- Cell proliferation and apoptosis assays (CCK-8, BrdU-ELISA, ApoTox-Glo™).
- Western blotting and luciferase reporter assays to validate target interaction.
Main Results:
- miR-139 expression was decreased, while FOXP2 expression was increased in OS tissues and cell lines.
- Lower miR-139 levels correlated with advanced tumor stage and metastasis.
- miR-139 overexpression inhibited cell proliferation and induced apoptosis by targeting FOXP2.
Conclusions:
- miR-139 acts as a tumor suppressor in OS by targeting FOXP2.
- miR-139 may serve as a potential diagnostic or predictive biomarker for osteosarcoma.
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