Circular RNAs Modulate Hippo-YAP Signaling: Functional Mechanisms in Cancer

Overview

Journal Theranostics

Date 2022 Jun 8

PMID 35673576

Authors

Javeria Qadir

Feiya Li

Burton B Yang

Affiliations

Soon will be listed here.

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.

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References

Li F, Yang Q, He A, Yang B . Circular RNAs in cancer: Limitations in functional studies and diagnostic potential. Semin Cancer Biol. 2020; 75:49-61. DOI: 10.1016/j.semcancer.2020.10.002. View

Li Z, Chen Z, Hu G, Jiang Y . Roles of circular RNA in breast cancer: present and future. Am J Transl Res. 2019; 11(7):3945-3954. PMC: 6684920. View

Cai W, Ji J, Wu B, Hao K, Ren P, Jin Y . Characterization of the small RNA transcriptomes of cell protrusions and cell bodies of highly metastatic hepatocellular carcinoma cells via RNA sequencing. Oncol Lett. 2021; 22(1):568. PMC: 8185705. DOI: 10.3892/ol.2021.12829. View

Zhang H, Meng F, Dong S . circSMARCA5 Promoted Osteosarcoma Cell Proliferation, Adhesion, Migration, and Invasion through a Competing Endogenous RNA Network. Biomed Res Int. 2020; 2020:2539150. PMC: 7537690. DOI: 10.1155/2020/2539150. View

Zhang M, Jia L, Zheng Y . circRNA Expression Profiles in Human Bone Marrow Stem Cells Undergoing Osteoblast Differentiation. Stem Cell Rev Rep. 2018; 15(1):126-138. DOI: 10.1007/s12015-018-9841-x. View

Rao A, Arvinden V, Ramasamy D, Patel K, Meenakumari B, Ramanathan P . Identification of novel dysregulated circular RNAs in early-stage breast cancer. J Cell Mol Med. 2021; 25(8):3912-3921. PMC: 8051735. DOI: 10.1111/jcmm.16324. View

Ashwal-Fluss R, Meyer M, Pamudurti N, Ivanov A, Bartok O, Hanan M . circRNA biogenesis competes with pre-mRNA splicing. Mol Cell. 2014; 56(1):55-66. DOI: 10.1016/j.molcel.2014.08.019. View

Smith A, Sompel K, Elango A, Tennis M . Non-Coding RNA and Frizzled Receptors in Cancer. Front Mol Biosci. 2021; 8:712546. PMC: 8521042. DOI: 10.3389/fmolb.2021.712546. View

Du W, Xu J, Yang W, Wu N, Li F, Zhou L . A Neuroligin Isoform Translated by circNlgn Contributes to Cardiac Remodeling. Circ Res. 2021; 129(5):568-582. DOI: 10.1161/CIRCRESAHA.120.318364. View

10.

Zhao X, Cai Y, Xu J . Circular RNAs: Biogenesis, Mechanism, and Function in Human Cancers. Int J Mol Sci. 2019; 20(16). PMC: 6720291. DOI: 10.3390/ijms20163926. View

11.

Li S, Li J, Zhang H, Zhang Y, Wang X, Yang H . Gastric cancer derived exosomes mediate the delivery of circRNA to promote angiogenesis by targeting miR-29a/VEGF axis in endothelial cells. Biochem Biophys Res Commun. 2021; 560:37-44. DOI: 10.1016/j.bbrc.2021.04.099. View

12.

Robic A, Kuhn C . Beyond Back Splicing, a Still Poorly Explored World: Non-Canonical Circular RNAs. Genes (Basel). 2020; 11(9). PMC: 7565381. DOI: 10.3390/genes11091111. View

13.

Chen L . The biogenesis and emerging roles of circular RNAs. Nat Rev Mol Cell Biol. 2016; 17(4):205-11. DOI: 10.1038/nrm.2015.32. View

14.

Fang X, Wen J, Sun M, Yuan Y, Xu Q . CircRNAs and its relationship with gastric cancer. J Cancer. 2019; 10(24):6105-6113. PMC: 6856571. DOI: 10.7150/jca.32927. View

15.

Wang Y, Wang Z . Efficient backsplicing produces translatable circular mRNAs. RNA. 2014; 21(2):172-9. PMC: 4338345. DOI: 10.1261/rna.048272.114. View

16.

Chen L, Shan G . CircRNA in cancer: Fundamental mechanism and clinical potential. Cancer Lett. 2021; 505:49-57. DOI: 10.1016/j.canlet.2021.02.004. View

17.

Chen H, Zhang X, Peng Z, Xing Z, Zhang Y, Li Y . The circular RNA circSlc7a11 promotes bone cancer pain pathogenesis in rats by modulating LLC-WRC 256 cell proliferation and apoptosis. Mol Cell Biochem. 2021; 476(4):1751-1763. PMC: 7940317. DOI: 10.1007/s11010-020-04020-1. View

18.

Deng Y, Min Y, Zhou K, Yang Q, Peng M, Cui Z . Identification of the tumor‑suppressive role of circular RNA‑FOXO3 in colorectal cancer via regulation of miR‑543/LATS1 axis. Oncol Rep. 2021; 46(5). PMC: 8485021. DOI: 10.3892/or.2021.8190. View

19.

Wu N, Yuan Z, Du K, Fang L, Lyu J, Zhang C . Translation of yes-associated protein (YAP) was antagonized by its circular RNA via suppressing the assembly of the translation initiation machinery. Cell Death Differ. 2019; 26(12):2758-2773. PMC: 7224378. DOI: 10.1038/s41418-019-0337-2. View

20.

Zygulska A, Krzemieniecki K, Pierzchalski P . Hippo pathway - brief overview of its relevance in cancer. J Physiol Pharmacol. 2017; 68(3):311-335. View