Pediatric cancer treatments: new possibilities coming from RNA-based regulatory mechanism
Scientific interest in circular RNAs (circRNAs) is increasing due to the peculiar characteristics of this emerging class of molecules and their functions in various pathological conditions, including cancer.
New research carried out in the Department of Biology and Biotechnology "Charles Darwin" at Sapienza University, in collaboration with the Italian Institute of Technology (IIT), has unveiled a novel molecular mechanism underlying the regulation of several protein expressions: the interaction between RNA molecules, particularly between a circular RNA, circZNF609, and some messenger RNAs. Researchers at Sapienza found that, in a specific case, the interaction between circZNF609 and the mRNA encoding the CKAP5 protein, involved in cell division control, regulates the proliferative potential of rhabdomyosarcoma.
This discovery, published in Molecular Cell journal and funded by the AIRC Foundation for Cancer Research, represents a further advance in the elucidation of the different roles of RNA in the cell and, particularly, identifies a new relevant function of circular RNA molecules.
The study revealed how this molecular mechanism modulates the growth of rhabdomyosarcoma, one of the most common malignant tumours in children, classified among the so-called soft tissue sarcomas, tumours that develop from muscles, fat or connective tissue.
"By preventing the interaction between the two RNA molecules, we were able to make cancer cells more responsive to various chemotherapeutics generally used in the treatment of rhabdomyosarcoma - says Irene Bozzoni from Sapienza University, corresponding author, - but often inefficient in the most serious cases".
It has also been shown that this molecular mechanism also works in other cancers, such as chronic myeloid leukaemia and neuroblastoma, making this circuit an interesting candidate for new RNA-based medical therapies.
These results underline the importance of studying the interactions between non-coding RNAs and mRNAs to identify new regulatory mechanisms controlling fundamental cellular processes.
Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity - Francesca Rossi, Manuel Beltran, Michela Damizia, Chiara Grelloni, Alessio Colantoni, Adriano Setti, Gaia Di Timoteo, Dario Dattilo, Alvaro Centrón-Broco, Carmine Nicoletti, Maurizio Fanciulli, Patrizia Lavia, Irene Bozzoni - Mol. Cell 2021 https://doi.org/10.1016/j.molcel.2021.11.032
Department of Biology and Biotechnology "Charles Darwin"