Recent progress of circular RNAs in different types of human cancer: Technological landscape, clinical opportunities and challenges (Review)

Abstract

Circular RNAs (circRNAs) are a novel class of endogenous non-coding RNAs that have been recently regarded as functionally active. CircRNAs are remarkably stable and known to possess several biological functions such as microRNA sponging, regulating transcription and splicing and occasionally acting as polypeptide-producing templates. CircRNAs show tissue-specific expression and have been reported to be associated with the progression of several types of malignancies. Given the recent progress in genome sequencing and bioinformatics techniques, a rapid increment in the biological role of circRNAs has been observed. Concurrently, the patent search from different patent databases shows that the patent number of circRNA is increasing very quickly. These phenomena reveal a rapid development of the technological landscape. In the present review, the recent progress on circRNAs in various kinds of cancer has been investigated and their function as biomarkers or therapeutic targets and their technological landscape have been appreciated. A new insight into circRNAs structure and functional capabilities in cancer has been reviewed. Continually increasing knowledge on their critical role during cancer progression is projecting them as biomarkers or therapeutic targets for various kinds of cancer. Thus, recent updates on the functional role of circRNAs in terms of the technological landscape, clinical opportunities (biomarkers and therapeutic targets), and challenges in cancer have been illustrated.

The interplay between noncoding RNA and YAP/TAZ signaling in cancers: molecular functions and mechanisms

“…These structural characteristics increase the stability of circRNAs in plasma and other body fluids; thus, they are potential diagnostic and prognostic biomarkers in cancer. CircRNAs can modify various biological activities, for example, regulating transcription and degradation and occasionally acting as polypeptide-producing templates [ 152 ]. In addition, like lncRNAs, circRNAs can sponge miRNAs.…”

Current advances in our understanding of circular RNA (circRNA) in Alzheimer’s disease (AD); the potential utilization of synthetic circRNAs as a therapeutic strategy in the clinical management of AD

“…Due to a lack of free 3′ or 5′ ends, circRNAs are not directly targeted and inactivated by abundant cellular endo-and exonuclases and as such are remarkably stable information-rich ssRNA entities (Memczak et al, 2013;Guo et al, 2014;Zhao et al, 2016;Rybak-Wolf and Plass 2021). Abundant evidence has accumulated that circRNAs possess several biological functions including miRNA sponging, roles in transcriptional regulation, the specific splicing of heterogeneous nuclear RNA (hnRNA) and have capability to act as polypeptide-generating templates (Zhao et al, 2016;Lauretti et al, 2021;Nisar et al, 2021;Rybak-Wolf and Plass 2021;Sharma et al, 2022;Sinha et al, 2022;Wang et al, 2022;Zhang et al, 2022). Emerging data further indicates that circRNAs play important and determinant roles in both health and disease ranging from acute CNS injuries including ischemic stroke and traumatic brain injury to cancer and AD (Salzman et al, 2012;Hansen et al, 2013;Memczak et al, 2013;Lukiw 2022;Sharma et al, 2022;Sinha et al, 2022;Zhang et al, 2022).…”

“…Abundant evidence has accumulated that circRNAs possess several biological functions including miRNA sponging, roles in transcriptional regulation, the specific splicing of heterogeneous nuclear RNA (hnRNA) and have capability to act as polypeptide-generating templates (Zhao et al, 2016;Lauretti et al, 2021;Nisar et al, 2021;Rybak-Wolf and Plass 2021;Sharma et al, 2022;Sinha et al, 2022;Wang et al, 2022;Zhang et al, 2022). Emerging data further indicates that circRNAs play important and determinant roles in both health and disease ranging from acute CNS injuries including ischemic stroke and traumatic brain injury to cancer and AD (Salzman et al, 2012;Hansen et al, 2013;Memczak et al, 2013;Lukiw 2022;Sharma et al, 2022;Sinha et al, 2022;Zhang et al, 2022). Although circRNAs may take many forms that include coding and non-coding RNA (ncRNA) sequences and vary widely in individual abundance, speciation, size and complexity this current paper will focus on circRNAs containing miRNA-and anti-miRNA-type regulatory sequences for which a relatively large amount of basic research has already been completed.…”

“…Compared to linear ssRNA, circRNAs are produced differentially by back-splicing exons or lariat introns from immature pre-microRNA (pre-miRNA) or pre-messenger RNA (mRNA) templates (Hansen et al, 2013;Memczak et al, 2013;Salzman et al, 2013;Enuka et al, 2016;Lauretti et al, 2021;Nisar et al, 2021;Zhang et al, 2022). This biologically heterogeneous circRNA exhibiting cell-and tissue-specific expression patterns suggest multifaceted circRNA roles: 1) in the assembly of RNA binding protein (RBP) and ribonucleprotein (RNP) complexes; 2) as circular templates for potentially rapid translation, splicing and translation-event regulators; 3) occasionally acting as polypeptide-producing templates; and 4) as modulators of RNA transcriptomic function in part as miRNA 'sponging' leading to the inactivation and/or availability of free miRNA species (Lauretti et al, 2021;Nisar et al, 2021;Sharma et al, 2022;Zhang et al, 2022). To date the best characterized circRNA functions are associated with miRNA regulation (Salzman et al, 2012;Hansen et al, 2013;Memczak et al, 2013;Salzman et al, 2013;Jeck and Sharpless 2014;Zhao et al, 2016;Akhter 2018;Nisar et al, 2021;Rybak-Wolf and Plass, 2021;Sharma et al, 2022;Sinha et al, 2022;Zhang et al, 2022).…”

“…This biologically heterogeneous circRNA exhibiting cell-and tissue-specific expression patterns suggest multifaceted circRNA roles: 1) in the assembly of RNA binding protein (RBP) and ribonucleprotein (RNP) complexes; 2) as circular templates for potentially rapid translation, splicing and translation-event regulators; 3) occasionally acting as polypeptide-producing templates; and 4) as modulators of RNA transcriptomic function in part as miRNA 'sponging' leading to the inactivation and/or availability of free miRNA species (Lauretti et al, 2021;Nisar et al, 2021;Sharma et al, 2022;Zhang et al, 2022). To date the best characterized circRNA functions are associated with miRNA regulation (Salzman et al, 2012;Hansen et al, 2013;Memczak et al, 2013;Salzman et al, 2013;Jeck and Sharpless 2014;Zhao et al, 2016;Akhter 2018;Nisar et al, 2021;Rybak-Wolf and Plass, 2021;Sharma et al, 2022;Sinha et al, 2022;Zhang et al, 2022). CircRNAs have been implicated in many incapacitating human diseases due to their aberrant expression under different pathological conditions.…”