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Updated: Nov 10, 2025

Three-Dimensional Bone Extracellular Matrix Model for Osteosarcoma
Published on: April 12, 2019
Circ_WWC3 overexpression decelerates the progression of osteosarcoma by regulating miR-421/PDE7B axis
Sihai Liu1, Jing Zhang2, Ting Zheng3
1Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Wuhan, Hubei, 430060, China.
Background:
Emerging evidence has shown that circular RNAs (circRNAs) are vital regulators in osteosarcoma (OS) progression. However, the effects of circ_WWC3 in OS have not been explored. In this research, the functions and mechanisms of circ_WWC3 in OS were investigated.
Methods:
Quantitative reverse trancription polymerase chain reaction (qRT-PCR) was adopted to determine the levels of circ_WWC3, WW and WWC3 mRNA, miR-421, and phosphodiesterase 7B (PDE7B) mRNA. RNase R assay was used to determine the characteristic of circ_WWC3. Colony formation assay and 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide (MTT) assay were applied for cell growth. Transwell assay was performed for cell migration and invasion. Flow cytometry analysis was utilized for cell apoptosis. Western blot assay was conducted for the levels of apoptosis-related proteins and PDE7B protein. Dual-luciferase reporter assay was carried out to analyze the targeting relationship between miR-421 and circ_WWC3 or PDE7B. The murine xenograft model was established to explore the effect of circ_WWC3 in vivo.
Results:
Compared to normal tissues and cells, circ_WWC3 and PDE7B were downregulated in OS tissues and cells. Overexpression of circ_WWC3 or PDE7B suppressed OS cell growth, migration, and invasion and promoted apoptosis in vitro. Regarding the mechanism analysis, circ_WWC3 positively modulated PDE7B expression by targeting miR-421. MiR-421 overexpression restored the impacts of circ_WWC3 on OS cell growth, metastasis, and apoptosis. Inhibition of miR-421 repressed the malignant behaviors of OS cells by targeting PDE7B. In addition, circ_WWC3 inhibited the tumorigenicity of OS in vivo.
Conclusion:
Circ_WWC3 overexpression slowed the development of OS by elevating PDE7B via sponging miR-421.
Insights
Circular RNA circ_WWC3 inhibits osteosarcoma (OS) progression by increasing PDE7B levels through sponging miR-421. This finding offers a potential therapeutic target for OS treatment.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Circular RNAs (circRNAs) are increasingly recognized as key regulators in osteosarcoma (OS) development.
- The specific role of circ_WWC3 in OS progression remained largely unexplored prior to this study.
Purpose of the Study:
- To investigate the functional role and underlying molecular mechanisms of circ_WWC3 in osteosarcoma.
Main Methods:
- Quantitative reverse transcription polymerase chain reaction (qRT-PCR) and RNase R assay were used to quantify RNA levels.
- Cellular assays including colony formation, MTT, Transwell, and flow cytometry assessed proliferation, migration, invasion, and apoptosis.
- Western blot analyzed protein expression, while dual-luciferase reporter assays elucidated miRNA-target interactions.
- A murine xenograft model was employed for in vivo validation.
Main Results:
- circ_WWC3 and PDE7B were found to be downregulated in OS tissues and cells compared to normal controls.
- Overexpression of circ_WWC3 or PDE7B inhibited OS cell proliferation, migration, and invasion, while promoting apoptosis in vitro.
- circ_WWC3 positively regulated PDE7B by sponging miR-421, and miR-421 overexpression reversed the effects of circ_WWC3.
- Inhibition of miR-421 promoted malignant behaviors by targeting PDE7B, and circ_WWC3 suppressed tumor growth in vivo.
Conclusions:
- circ_WWC3 acts as a tumor suppressor in osteosarcoma.
- Overexpression of circ_WWC3 inhibits OS development by upregulating PDE7B through the sponging of miR-421.
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