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Cross-Talk Between circRNAs and mRNAs Modulates MiRNA-mediated Circuits and Affects Melanoma Plasticity

  • Maria Rita Fumagalli
  • Maria Chiara Lionetti
  • Stefano Zapperi
  • Caterina A. M. La PortaEmail author
Original Article

Abstract

CircularRNAs (circRNAs) are non-coding RNAs which compete for microRNA (miRNA) binding, influencing the abundance and stability of other RNA species. Herein we have investigated the effect of circRNAs on the mir200-ZEB1 feedback loop in relationship with the aggressiveness of human melanoma cells. We first compared the level of expression of key factors in the mir200-ZEB1 feedback loop in primary human melanoma cells compared with their matching metastatic one and found a correlation between the aggressiveness of the cells and the level of expression of ZEB1 and SNAI1. We also analyzed factors in the mir200-ZEB1 feedback loop, including circZEB1, during the phenotypic switching of human melanoma cells. Our results showed a correlation between the level of ZEB1 and SNAI1 and the fraction of cancer stem cells in the population. The level of circZEB1 was, however, consistently high during the entire phenotypic transformation. To understand this result we propose a mathematical model of the regulatory circuit. According to the model, the experimental observations can be explained by the presence of a back-splicing factor limiting circRNA production.

Keywords

circRNA ZEB1 Melanoma Phenotypic switching 

Notes

Acknowledgments

The project was supported by funded from the Center for Complexity and Biosystems of UniMI. The research leading to these results was funded by AIRC under IG2018-ID 21558 project-PI Pusch Michael.

Supplementary material

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Copyright information

© Springer Nature B.V. 2019

Authors and Affiliations

  1. 1.Consiglio Nazionale delle RicercheIstituto di BiofisicaMilanoItaly
  2. 2.Center for Complexity and Biosystems, Department of Environmental Science and PolicyUniversity of MilanMilanoItaly
  3. 3.Center for Complexity and Biosystems, Department of PhysicsUniversity of MilanoMilanoItaly
  4. 4.CNR - Consiglio Nazionale delle RicercheIstituto di Chimica della Materia Condensata e di Tecnologie per l’EnergiaMilanoItaly
  5. 5.Consiglio Nazionale delle RicercheIstituto di BiofisicaMilanoItaly

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