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Updated: Jan 23, 2026

Identification of Circular RNAs using RNA Sequencing
Published on: November 14, 2019
The circular RNA circ-Ccnb1 dissociates Ccnb1/Cdk1 complex suppressing cell invasion and tumorigenesis
Ling Fang1, William W Du2, Faryal Mehwish Awan3
1Sunnybrook Research Institute, Toronto, Canada; China-Japan Union Hospital of Jilin University, Jilin, China.
Abstract:
Circular RNAs represent a large class of non-coding RNAs that are extensively expressed in mammals. However, the functions of circular RNAs are largely unknown. We recently reported that the circular RNA circ-Ccnb1 could bind with H2AX in p53 mutant cells and suppressed mutant p53 in tumor progression. Here we found that circ-Ccnb1 could interact with both Ccnb1 and Cdk1 proteins. Normally, Ccnb1 and Cdk1 proteins form a complex, allowing Ccnb1 to function as an all-or-none switch for cell mitosis. The interaction of circ-Ccnb1 with Ccnb1 and Cdk1 proteins dissociated the formation of Ccnb1-Cdk1 complex, by forming a large complex containing circ-Ccnb1, Ccnb1 and Cdk1. Formation of this large complex may occur in cytosol and nuclei, and Ccnb1 loses its roles in enhancing cell migration, invasion, proliferation and survival. In vivo, ectopic delivery of circ-Ccnb1 inhibited tumor growth and extended mouse viability. These results have added another layer of mechanisms for circ-Ccnb1 to regulate tumor progression in vitro and in vivo.
Insights
Circular RNA circ-Ccnb1 disrupts the Ccnb1-Cdk1 complex, inhibiting cell functions crucial for tumor growth. This finding reveals a new mechanism by which circ-Ccnb1 regulates tumor progression in vitro and in vivo.
Area of Science:
- Molecular Biology
- Cancer Biology
- RNA Biology
Background:
- Circular RNAs (circRNAs) are a vast class of non-coding RNAs in mammals with largely unknown functions.
- Previous research identified circ-Ccnb1 binding to H2AX in p53 mutant cells, suppressing tumor progression.
- The precise molecular mechanisms underlying circRNA functions, particularly in cancer, require further elucidation.
Purpose of the Study:
- To investigate the interaction of circ-Ccnb1 with key cell cycle proteins.
- To elucidate the role of circ-Ccnb1 in regulating the Ccnb1-Cdk1 complex and its downstream effects on cancer progression.
- To evaluate the therapeutic potential of circ-Ccnb1 in inhibiting tumor growth in vivo.
Main Methods:
- Co-immunoprecipitation assays to detect interactions between circ-Ccnb1, Ccnb1, and Cdk1.
- Cellular localization studies to determine where the circ-Ccnb1 complex forms.
- Functional assays assessing cell migration, invasion, proliferation, and survival.
- In vivo studies involving ectopic delivery of circ-Ccnb1 to assess tumor growth inhibition and survival benefits in mice.
Main Results:
- Circ-Ccnb1 was found to interact with both Ccnb1 and Cdk1 proteins.
- The interaction of circ-Ccnb1 with Ccnb1 and Cdk1 disrupted the formation of the canonical Ccnb1-Cdk1 complex, creating a larger circ-Ccnb1-Ccnb1-Cdk1 complex.
- This disruption led to the loss of Ccnb1's functions in promoting cell migration, invasion, proliferation, and survival.
- Ectopic delivery of circ-Ccnb1 significantly inhibited tumor growth and improved mouse survival in vivo.
Conclusions:
- Circ-Ccnb1 acts as a novel regulator of the cell cycle by interfering with the Ccnb1-Cdk1 complex.
- The disruption of the Ccnb1-Cdk1 complex by circ-Ccnb1 provides a new mechanism for controlling cancer cell phenotypes.
- Circ-Ccnb1 demonstrates therapeutic potential for inhibiting tumor progression and warrants further investigation as an anti-cancer agent.
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