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Updated: Oct 2, 2025

Analysis of Combinatorial miRNA Treatments to Regulate Cell Cycle and Angiogenesis
Published on: March 30, 2019
Silencing of circ-CDK14 suppresses osteosarcoma progression through the miR-198/E2F2 axis
Jun Liu1, Jianwen Zhao2, Guang Feng3
1Department of Hand Surgery, The Second Hospital of Jilin University, Changchun, 130000, China.
Background:
Osteosarcoma (OS) is the most common primary bone malignancy. Circular RNAs (circRNAs) have been implicated in OS pathogenesis. In the current study, we explored the precise role of circRNA cyclin dependent kinase 14 (circ-CDK14, hsa_circ_0001721) in OS progression.
Methods:
The levels of circ-CDK14, miR-198 and E2F transcription factor 2 (E2F2) were evaluated by quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot. Cell viability, apoptosis, migration and invasion were determined using the Cell Counting-8 Kit (CCK-8), flow cytometry and transwell assays, respectively. Glucose consumption, lactate production and adenosine triphosphate (ATP) level were gauged using the commercial assay kits. The direct relationship between miR-198 and circ-CDK14 or E2F2 was confirmed by dual-luciferase reporter, RNA pull-down and RNA immunoprecipitation (RIP) assays. Animal studies were used to analyze the role of circ-CDK14 in vivo.
Results:
Our data revealed that circ-CDK14 was up-regulated and miR-198 was down-regulated in OS tissues and cell lines. Circ-CDK14 silencing suppressed OS cell viability, migration, invasion, and glycolysis and promoted cell apoptosis in vitro, as well as diminished tumor growth in vivo. Mechanistically, circ-CDK14 directly targeted miR-198. Moreover, miR-198 was a functional mediator of circ-CDK14 in regulating OS cell progression in vitro. E2F2 was a direct target of miR-198, and miR-198 overexpression regulated OS cell progression in vitro by down-regulating E2F2. Furthermore, circ-CDK14 regulated E2F2 expression by functioning as a sponge of miR-198 in OS cells.
Conclusion:
Our findings demonstrate the inhibitory effect of circ-CDK14 silencing on OS progression by targeting the miR-198/E2F2 axis, establishing a strong rationale for decreasing circ-CDK14 as a novel therapeutic strategy for OS.
Insights
Circular RNA cyclin dependent kinase 14 (circ-CDK14) promotes osteosarcoma (OS) progression by targeting the miR-198/E2F2 pathway. Silencing circ-CDK14 inhibits OS cell growth and metastasis, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma (OS) is the most common primary bone cancer.
- Circular RNAs (circRNAs) play a role in OS development.
- The specific function of circRNA cyclin dependent kinase 14 (circ-CDK14) in OS is under investigation.
Purpose of the Study:
- To investigate the role of circ-CDK14 in osteosarcoma progression.
- To elucidate the underlying molecular mechanisms involving miR-198 and E2F2.
- To evaluate circ-CDK14 as a potential therapeutic target for OS.
Main Methods:
- Quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot to measure molecule levels.
- Cell Counting-8 Kit (CCK-8), flow cytometry, and transwell assays to assess cell behavior.
- Dual-luciferase reporter, RNA pull-down, and RNA immunoprecipitation (RIP) assays to confirm molecular interactions.
- In vivo animal studies to evaluate therapeutic efficacy.
Main Results:
- Circ-CDK14 was upregulated, while miR-198 was downregulated in OS tissues and cell lines.
- Circ-CDK14 silencing inhibited OS cell viability, migration, invasion, and glycolysis, and promoted apoptosis.
- Circ-CDK14 directly targeted miR-198, which in turn targeted E2F2, forming a circ-CDK14/miR-198/E2F2 axis.
- Circ-CDK14 knockdown suppressed tumor growth in vivo.
Conclusions:
- Circ-CDK14 promotes osteosarcoma progression through the miR-198/E2F2 pathway.
- Silencing circ-CDK14 exhibits inhibitory effects on OS.
- Circ-CDK14 represents a promising novel therapeutic strategy for osteosarcoma.
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