Circular RNAs in cell cycle regulation: Mechanisms to clinical significance

Abstract

Circular RNAs (circRNAs), a type of non‐coding RNA, are single‐stranded circularized molecules characterized by high abundance, evolutionary conservation and cell development‐ and tissue‐specific expression. A large body of studies has found that circRNAs exert a wide variety of functions in diverse biological processes, including cell cycle. The cell cycle is controlled by the coordinated activation and deactivation of cell cycle regulators. CircRNAs exert mutifunctional roles by regulating gene expression via various mechanisms. However, the functional relevance of circRNAs and cell cycle regulation largely remains to be elucidated. Herein, we briefly describe the biogenesis and mechanistic models of circRNAs and summarize their functions and mechanisms in the regulation of critical cell cycle modulators, including cyclins, cyclin‐dependent kinases and cyclin‐dependent kinase inhibitors. Moreover, we highlight the participation of circRNAs in cell cycle‐related signalling pathways and the clinical value of circRNAs as promising biomarkers or therapeutic targets in diseases related to cell cycle disorder.

Wnt/β-Catenin Signaling as a Driver of Hepatocellular Carcinoma Progression: An Emphasis on Molecular Pathways

“… 222 CircRNAs are stable in multiple tissues and body fluids. 217 , 223 They lack protein encoding capacity and they have a closed loop structure. 224 Recent studies have revealed the role of circRNAs in HCC.…”

Emerging Role and Mechanism of circRNAs in Pediatric Malignant Solid Tumors

“…CircRNAs are formed by splicing of precursor mRNAs (pre-mRNAs) and are mostly endogenous. They have no 3′ tail or 5′ cap end and are covalently closed loops ( Qu et al, 2015 ; Meng et al, 2017 ) formed by lasso-driven cyclization, direct reverse splicing, or exon skipping, or they can be cyclized by intron pairing ( Wang et al, 2021e ; Xiao et al, 2021 ). In addition, circRNAs can also be formed by RNA binding proteins (RBPs)-mediated cyclization joining the downstream 5′ end donor site to the upstream 3′ end acceptor site to form a single-stranded covalent closed-loop that joins the remaining sequence after removal of the intron ( Ali et al, 2021 ; Wang et al, 2021d ).…”

“…Many circRNAs that are highly expressed in blood have relatively low expression of their corresponding linear RNAs ( Rahmati et al, 2021 ; Xiao et al, 2021 ). The unique functions and properties of circRNAs make them of great clinical potential in life sciences and medicine ( Gu et al, 2021 ; Yi et al, 2021 ).…”

Noncoding RNAs of Extracellular Vesicles in Tumor Angiogenesis: From Biological Functions to Clinical Significance

“…Exosomes, small EVs, play a crucial role in intercellular communication by transporting proteins, mRNAs, and ncRNAs [2]. In the past decade, ncRNAs, including mi-croRNAs (miRNAs), PIWI-interacting RNAs (piRNAs), long noncoding RNAs (lncRNAs), and circular RNAs (circRNAs), have been intensively studied in many human diseases, particularly cancers [3][4][5][6]. Studies have indicated that exosomal ncRNAs acting as versatile regulators at the transcriptional and post-transcriptional levels may contribute to cancer progression and metastasis [7,8].…”