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Circular RNA hsa_circ_0000658 inhibits osteosarcoma cell proliferation and migration via the miR-1227/IRF2 axis
Abstract:
Osteosarcoma (OS) is the most frequently occurring bone cancer. Circular RNAs (circRNAs) have been shown to exert pivotal impact in modulation of gene expression, but their roles in OS are still not fully understood. In this study, we analysed the role of circ-0000658 in OS. Thereafter, molecular techniques such as Western blot, qRT-PCR, RNA-binding protein immunoprecipitation and Dual-Luciferase reporter assays were implemented to investigate the role of circ-0000658/miR-1227/interferon regulatory factor-2 (IRF2) axis in OS. Eventually, the impact of circ-0000658 on tumour growth and metastasis was observed in a xenograft mouse model. The results of this study revealed that circ-0000658 exhibits low levels in OS tissues and cell lines. Moreover, circ-0000658 repression promoted cell cycle, proliferation, invasion and migration but inhibited the apoptosis of OS cells. Researches have previously shown that circ-0000658 contains a binding site for miR-1227 and thus can abundantly sponge miR-1227 to up-regulate the expression of its target gene IRF2. Moreover, both inhibition of miR-1227 and overexpression of IRF2 reversed cell proliferation and invasion, which was triggered by circ-0000658 repression. Conclusively, circ-0000658 modulates biological function of OS cells through the miR-1227/IRF2 axis. Therefore, circ-0000658 might act as a possible novel therapeutic target for the treatment of OS.
Insights
Circular RNAs (circRNAs) like circ-0000658 are crucial in osteosarcoma (OS). This study found circ-0000658 inhibits OS progression by regulating the miR-1227/IRF2 axis, suggesting it as a potential therapeutic target.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Osteosarcoma (OS) is the most common primary bone cancer.
- Circular RNAs (circRNAs) regulate gene expression, but their role in OS is not fully understood.
Purpose of the Study:
- To investigate the role of circ-0000658 in osteosarcoma (OS).
- To elucidate the molecular mechanism of circ-0000658 in OS progression via the miR-1227/interferon regulatory factor-2 (IRF2) axis.
Main Methods:
- Western blot and qRT-PCR to assess protein and RNA levels.
- RNA-binding protein immunoprecipitation and Dual-Luciferase reporter assays to confirm interactions.
- Xenograft mouse models to evaluate tumor growth and metastasis.
Main Results:
- circ-0000658 levels were significantly lower in OS tissues and cell lines.
- circ-0000658 repression promoted cell cycle, proliferation, invasion, and migration while inhibiting apoptosis.
- circ-0000658 sponged miR-1227, up-regulating IRF2 expression.
Conclusions:
- circ-0000658 acts as a tumor suppressor in OS by modulating the miR-1227/IRF2 axis.
- circ-0000658 may serve as a novel therapeutic target for osteosarcoma treatment.
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