Circular RNAs (circRNAs), which are generated mainly from back-splicing of exons in precursor mRNAs (pre-mRNAs), are a novel class of endogenous covalently closed RNA molecules. Their functions as microRNA sponges, protein scaffolds, and modulators of transcription and splicing, as well as occasional templates for polypeptide production, are beginning to be recognized, though the investigation of circRNAs is in its infancy. circRNAs play critical roles in diverse cellular processes. Aberrant expression of circRNAs in malignancies sustains cellular growth and proliferation, promotes cellular invasiveness, and circumvents cellular senescence and death, suggesting their potential for exploitation as clinical biomarkers and therapeutic targets. In this review, we highlight recent progress in research on circRNAs in cancer, emphasizing the molecular mechanisms and potential clinical value of circRNAs.

Circular RNAs (circRNAs) are a novel class of endogenous noncoding RNAs (ncRNAs) with a covalently closed loop structure. Accumulating evidence shows that circRNAs play vital roles in the growth, metastasis, treatment and prognosis of various cancers. However, the detailed functions and underlying mechanisms of circEVI5 (hsa_circ_0013162) in gastric cancer (GC) remain undocumented. In this study, the expression levels and prognostic value of circEVI5 were validated in GC tissue samples by using qRT-PCR. circEVI5 was significantly downregulated in GC tissues and cells, and low circEVI5 expression was correlated with poor prognosis. Next, in vitro CCK-8 assay, EdU incorporation assay, PI staining cell cycle assay, and in vivo xenograft mouse models were conducted to assess the functions of circEVI5. Gain of function experiments indicated that circEVI5 could inhibit GC cell proliferation and retard the cell cycle. Moreover, bioinformatics prediction showed that circEVI5 binds to miR-4793-3p, while FOXO1 may be a target of miR-4793-3p. Pull-down assays, RNA immunoprecipitation (RIP) assays, luciferase assays, and western blot were used to confirm the interactions between circEVI5, miR-4793-3p, and FOXO1. Functional assays demonstrated that circEVI5 suppressed the proliferation of GC by sponging miR-4793-3p and increasing FOXO1 expression levels. In conclusion, our study demonstrated that circEVI5 can bind miR-4793-3p as a ceRNA to eliminate the negative regulation of FOXO1, therefore suppressing GC proliferation.

Background Circular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC). Methods High-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n = 136) and validation set (n = 167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan–Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance. Results A total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647. Conclusions CircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724).

Circular RNA (circRNA) is a novel RNA molecule characterized by covalently closed loop structure. Since its discovery, researchers have shown that circRNA is not “splicing noise” but a participant of various pathophysiological processes through unique mechanisms. circIPO7, which was identified as an independent prognostic factor in gastric cancer (GC) patients, was downregulated in GC tissues and cells compared to paracarcinoma tissues and normal epithelial cells. circIPO7 overexpression significantly suppressed GC cell proliferation in vitro and in vivo. Mechanistically, circIPO7 directly binds with caprin-1, an RNA-binding protein involved in mRNA translation, sharing overlapping binding sites with G3BP1. Thus, the complex containing overexpressed circIPO7 blocked the caprin-1-G3BP1 interaction and dissociated caprin-1 and its target mRNAs (EGFR and mTOR) from ribosomes, resulting in their translational inhibition, followed by PI3K/AKT/mTOR pathway inactivation. We uncovered a novel molecular mechanism for circRNAs in GC development, identifying circIPO7 as a potential target for cancer treatment.

Background Circular RNAs (circRNAs) have attracted increasing attention in recent years for their potential application as disease biomarkers due to their high abundance and stability. In this study, we attempted to screen circRNAs that can be used to predict postoperative recurrence and survival in patients with gastric cancer (GC). Methods High-throughput RNA sequencing was used to identify differentially expressed circRNAs in GC patients with different prognoses. The expression level of circRNAs in the training set (n = 136) and validation set (n = 167) was detected by quantitative real-time PCR (qRT-PCR). Kaplan–Meier estimator, receiver operating characteristic (ROC) curve and cox regression analysis were used to evaluate the prognostic value of circRNAs on recurrence-free survival (RFS) and overall survival (OS) in GC patients. CeRNA network prediction, gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed for the circRNAs with prognostic significance. Results A total of 259 differentially expressed circRNAs were identified in GC patients with different RFS. We found two circRNAs (hsa_circ_0005092 and hsa_circ_0002647) that highly expressed in GC patients with good prognoses, and subsequently established a predictive model for postoperative recurrence and prognosis evaluation, named circPanel. Patients with circPanellow might have shorter recurrence-free survival (RFS) and overall survival (OS). We also performed circRNA-miRNA-mRNA network prediction and functional analysis for hsa_circ_0005092 and hsa_circ_0002647. Conclusions CircPanel has the potential to be a prognostic biomarker in GC patients with greater accuracy than a single circRNA and certain traditional tumor markers (e.g., CEA, CA19-9 and CA724).