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.

Cancer Letters
|June 15, 2019
PubMed

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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