Sunnybrook Research Institute, Sunnybrook Health Sciences Centre, Toronto, Canada.
Department of Biosciences, COMSATS University Islamabad, Islamabad, Pakistan.
Theranostics. 2022 May 16;12(9):4269-4287. doi: 10.7150/thno.71708. eCollection 2022.
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.
Hippo 信号通路是一个进化上保守的网络，它在哺乳动物中调节器官大小和组织稳态。该通路通过开启或关闭其抑制和/或转录模块来控制各种细胞功能，如生长、增殖、存活、凋亡和干性，从而调节靶基因的表达。Hippo 信号的改变与各种形式的癌症有关。越来越多的证据表明 Hippo 信号通路与非编码 RNA，特别是环状 RNA（circRNA）之间存在串扰。在这种情况下，本综述介绍了 Hippo 通路与各种形式癌症中相关 circRNA 之间的机制相互作用，以及这些 circRNA 通过 miRNA 海绵或蛋白结合机制作为肿瘤抑制因子或癌基因发挥作用的能力。此外，我们讨论了 circRNA 机制研究中的限制和局限性，同时强调了与 Hippo-YAP 通路相关的 circRNAs 在癌症中的作用的一些悬而未决的问题。最后，我们描述了这些 circRNA 作为诊断和预后生物标志物以及癌症治疗的分子热点的潜力。
