Theranostics 2022; 12(9):4269-4287. doi:10.7150/thno.71708 This issue


Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer

Javeria Qadir1,2,3, Feiya Li1,3, Burton B. Yang1,3✉

1. Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada
2. Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan
3. Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, Canada

This is an open access article distributed under the terms of the Creative Commons Attribution License ( See for full terms and conditions.
Qadir J, Li F, Yang BB. Circular RNAs modulate Hippo-YAP signaling: functional mechanisms in cancer. Theranostics 2022; 12(9):4269-4287. doi:10.7150/thno.71708. Available from

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Graphic abstract

The Hippo signaling pathway is an evolutionarily conserved network that regulates organ size and tissue homeostasis in mammals. This pathway controls various cell functions, such as growth, proliferation, survival, apoptosis, and stemness by switching 'on' or 'off' its inhibitory and/or transcriptional module, thereby regulating target gene(s) expression. Altered Hippo signaling has been implicated in various forms of cancers. Increasing evidence suggests cross-talk between the Hippo signaling pathway and non-coding RNAs, in particular circular RNAs (circRNAs). In this context, the current review presents the mechanistic interplay between the Hippo pathway and related circRNAs in various forms of cancers, along with the capabilities of these circRNAs to function either as tumor suppressors or oncogenes through miRNA sponging or protein binding mechanisms. Furthermore, we discuss the constraints and limitations in circRNA mechanistic studies while highlighting some outstanding questions regarding the roles of circRNAs associated with the Hippo-YAP pathway in cancer. Finally, we delineate the potential of these circRNAs to be employed as diagnostic and prognostic biomarkers, as well as molecular hotspots for cancer therapy.

Keywords: Hippo pathway, YAP, circular RNA, circRNA, signal transduction, cancer progression