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.
Keywords: E2F2; Glycolysis; Osteosarcoma (OS); circ-CDK14; miR-198.
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