Circular RNAs: implications of signaling pathways and bioinformatics in human cancer

Abstract

Circular RNAs (circRNAs) form a class of endogenous single-stranded RNA transcripts that are widely expressed in eukaryotic cells. These RNAs mediate post-transcriptional control of gene expression and have multiple functions in biological processes, such as transcriptional regulation and splicing. They serve predominantly as microRNA sponges, RNA-binding proteins, and templates for translation. More importantly, circRNAs are involved in cancer progression, and may serve as promising biomarkers for tumor diagnosis and therapy. Although traditional experimental methods are usually time-consuming and laborious, substantial progress has been made in exploring potential circRNA-disease associations by using computational models, summarized signaling pathway data, and other databases. Here, we review the biological characteristics and functions of circRNAs, including their roles in cancer. Specifically, we focus on the signaling pathways associated with carcinogenesis, and the status of circRNA-associated bioinformatics databases. Finally, we explore the potential roles of circRNAs as prognostic biomarkers in cancer.

Ferroptosis-associated circular RNAs: Opportunities and challenges in the diagnosis and treatment of cancer

“…In addition, they are not susceptible to degradation by exonucleases, as they lack 3′and 5′ends ( Zhang et al, 2014 ; Fontemaggi et al, 2021 ) ( Figure 2 ). CircRNA biogenesis is mediated by four main mechanisms: intron base-pairing-driven cyclization ( Figure 2A ), RBP-driven cyclization ( Figure 2B ), lariat-driven cyclization ( Figure 2C ), and Pre-tRNAs generate tricRNAs ( Figure 2D ) ( Wang et al, 2021a ; Hu et al, 2023 ; Harper et al, 2021 ). Circular RNAs are classified into three main types according to their constituents: ciRNA, EIciRNA and exonic circRNA, which account for 85% of circular RNAs ( Fontemaggi et al, 2021 ; Eger et al, 2018 ).…”

“…The most abundant base modification of m6A RNA promotes efficient initiation of circRNA protein translation in human cells. M6A-driven translation requires the initiation factor eukaryotic translation initiation factor 4 gamma 2 (EIF4G2) and the m6A reader YTH N6-methyladenosine RNA binding protein F3 (YTHDF3) and is enhanced by the methyltransferase methyltransferase 3, N6-adenosine-methyltransferase complex catalytic subunit (METTL3), inhibited by the demethylase alpha-ketoglutarate dependent dioxygenase (FTO), and upregulated in response to heat shock ( Hu et al, 2023 ; Yang et al, 2017 ; Lei et al, 2020 ) ( Figure 3E ). In the cytoplasm, the m6A-binding protein YTHDF1 promotes the translation of m6A-modified mRNA, and YTHDF2 accelerates the decay of m6A-modified transcripts ( Shi et al, 2017 ).…”

Role of Non-Coding RNAs in TGF-β Signalling in Glioma

“…The miRNAs, lncRNAs, and circRNAs are aberrantly expressed in GBM tumour tissues and regulate GBM pathogenesis (Tables 1-3) [57,65,67]. They play critical regulatory functions in cancer by acting as oncogenes or tumour suppressors [68][69][70][71]. They have the potential for use as clinical biomarkers and therapeutic targets for cancers, including GBM [72][73][74][75][76][77].…”

Modulation of cancer progression by circRNA/ NF-kB axis

“…The evidence supporting the potential role of circRNAs in cancer biology has grown in recent years. They act to control the behavioral phenotypes of tumors, including proliferation, migration, and invasion via numerous mechanisms involving microRNA sponging, transcriptional regulation, and protein interaction (18,19). Although the regulatory function of circRNAs in physiological processes is still unclear, a common circRNA-mediated mechanism that circRNAs operate as competitive endogenous RNAs (ceRNAs) of microRNAs (miRNAs) in tumorigenesis has been suggested (20).…”