Circular RNAs in Cancer: emerging functions in hallmarks, stemness, resistance and roles as potential biomarkers

Abstract

Circular RNAs (circRNAs) are a class of RNA molecules with closed loops and high stability. CircRNAs are abundantly expressed in eukaryotic organisms and exhibit both location-and step-specificity. In recent years, circRNAs are attracting considerable research attention attributed to their possible contributions to gene regulation through a variety of actions, including sponging microRNAs, interacting with RNA-binding proteins, regulating transcription and splicing, and protein translation. Growing evidence has revealed that circRNAs play critical roles in the development and progression of diseases, especially in cancers. Without doubt, expanding our understanding of circRNAs will enrich knowledge of cancer and provide new opportunities for cancer therapy. In this review, we provide an overview of the characteristics, functions and functional mechanisms of circRNAs. In particular, we summarize current knowledge regarding the functions of circRNAs in the hallmarks, stemness, resistance of cancer, as well as the possibility of circRNAs as biomarkers in cancer.

circRNA circ‐CCND1 promotes the proliferation of laryngeal squamous cell carcinoma through elevating CCND1 expression via interacting with HuR and miR‐646

“…15 Recent studies have shown that circRNA functions through different actions, including serving as 'miRNA sponge', regulation of transcription and splicing, interacting with RNA-binding protein, and even translating polypeptide. 16 The most extensively studied is circRNA as a competing endogenous RNA (ceRNA) to effectively sponge miRNA, for example, circ-HIPK3/miR-7 in colorectal cancer, 17 circ-EPSTI1/miR-942 in ovarian cancer, 18 circ-ANKS1B/ miR-148/152 in breast cancer 19 and circ-AMOTL1L/miR-193a-5p in prostate cancer. 20 It is well recognized that miRNA is a post-transcriptional regulator by decreasing mRNA stability or inhibiting translation via directly targeting gene 3′-UTR.…”

Circ_0038467 regulates lipopolysaccharide‐induced inflammatory injury in human bronchial epithelial cells through sponging miR‐338‐3p

“…To validate this, we determined the expression of circ_0038467 in LPS‐treated 16HBE cells, and our data demonstrated a striking upregulation of circ_0038467. Due to the closed loop structures with neither 5′ caps nor 3′ polyadenylated tails, circRNAs are resistant to RNase R . Using RNase R assays, we uncovered that circ_0038467 was indeed a circular transcript.…”

Regulation of circular RNA circNFATc3 in cancer cells alters proliferation, migration and oxidative phosphorylation

“…Emerging evidence suggests that circRNAs are involved in complicated functions; such as acting as endogenous RNAs to sponge miRNAs, protein decoys, protein translation, regulating expression of parental genes, modulating alternative splicing, regulating RNA-protein interactions, and acting as scaffolds in the assembly of protein complexes [12,[27][28][29][30].…”

“…circRNAs have been shown to be differentially regulated in human cancers, including breast, prostate, brain, bladder, colorectal, ovarian, liver and kidney as well as hematological malignancies. Thus, it is becoming increasingly clear that circRNAs have a significant role in cancer pathogenesis, and they are likely to affect several hallmarks of cancer [10,11] [12]. Understanding the functional role of circular RNA in cancer cell invasion, migration, tumor suppression provides new insights into cancer detection, oncogenesis, and cancer prevention, which is still elusive.…”