1. Circular RNA ZNF609/CKAP5 mRNA interaction regulates microtubule dynamics and tumorigenicity.
- Author
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Rossi F, Beltran M, Damizia M, Grelloni C, Colantoni A, Setti A, Di Timoteo G, Dattilo D, Centrón-Broco A, Nicoletti C, Fanciulli M, Lavia P, and Bozzoni I
- Subjects
- Animals, Antineoplastic Agents pharmacology, ELAV-Like Protein 1 genetics, ELAV-Like Protein 1 metabolism, Female, Gene Expression Regulation, Neoplastic, Humans, K562 Cells, Male, Mice, Nude, Microtubule-Associated Proteins genetics, Microtubules drug effects, Microtubules genetics, Microtubules pathology, Neoplasms drug therapy, Neoplasms genetics, Neoplasms pathology, RNA, Circular genetics, RNA, Messenger genetics, Signal Transduction, Tumor Burden, Xenograft Model Antitumor Assays, Mice, Carcinogenesis, Microtubule-Associated Proteins metabolism, Microtubules metabolism, Neoplasms metabolism, RNA, Circular metabolism, RNA, Messenger metabolism
- Abstract
Circular RNAs (circRNAs) are widely expressed in eukaryotes and are regulated in many biological processes. Although several studies indicate their activity as microRNA (miRNA) and protein sponges, little is known about their ability to directly control mRNA homeostasis. We show that the widely expressed circZNF609 directly interacts with several mRNAs and increases their stability and/or translation by favoring the recruitment of the RNA-binding protein ELAVL1. Particularly, the interaction with CKAP5 mRNA, which interestingly overlaps the back-splicing junction, enhances CKAP5 translation, regulating microtubule function in cancer cells and sustaining cell-cycle progression. Finally, we show that circZNF609 downregulation increases the sensitivity of several cancer cell lines to different microtubule-targeting chemotherapeutic drugs and that locked nucleic acid (LNA) protectors against the pairing region on circZNF609 phenocopy such effects. These data set an example of how the small effects tuned by circZNF609/CKAP5 mRNA interaction might have a potent output in tumor growth and drug response., Competing Interests: Declaration of interests The authors declare no competing interests., (Copyright © 2021 The Author(s). Published by Elsevier Inc. All rights reserved.)
- Published
- 2022
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