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Review
. 2021 Jul;35(7):e23866.
doi: 10.1002/jcla.23866. Epub 2021 Jun 7.

Translation role of circRNAs in cancers

Yaqin Lu  1 , Zhe Li  1 , Chen Lin  1 , Jian Zhang  2 , Zhisen Shen  2
Affiliations
Review

Translation role of circRNAs in cancers

Yaqin Lu et al. J Clin Lab Anal. 2021 Jul.

Abstract

Circular RNAs (circRNAs) constitute a class of covalently closed RNA molecules. With the continuous advancement of high-throughput sequencing technology and bioinformatics tools, many circRNAs have been identified in various human tissues and cell lines. Notably, recent studies have indicated that some circRNAs have translational functions. Internal ribosome entry sites and the N6-methyladenosine modification mediate cap-independent translation. This review describes these two translation mechanisms and verification methods at the molecular level. Databases (including ORF Finder, Pfam, BLASTp, CircRNADb, CircBase, CircPro, CircCode, IRESite, IRESbase) were used to analyze whether circRNAs have the structural characteristic of translation. CircRNA minigene reporter system containing green fluorescent protein (GFP) confirmed the translation potential of circRNAs. Also, we briefly summarize the roles of proteins/peptides encoded by circRNAs (circFBXW7, circFNDC3B, circLgr4, circPPP1R12A, circMAPK1, circβ-catenin, circGprc5a, circ-SHPRH, circPINTexon2, circAKT3) that have been verified thus far in human cancers (triple-negative breast cancer, colon cancer, gastric cancer, hepatocellular carcinoma, bladder cancer, glioblastoma). Those findings suggest circRNAs have a great implication in translation of the human genome.

Keywords: N6-methyladenosine; cancers; circular RNAs; internal ribosome entry sites; translation.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

FIGURE 1
FIGURE 1
Classification of circRNAs. CircRNAs are divided into circular intronic RNAs (ciRNAs), exonic circRNAs (ecircRNAs), and exon‐intronic circRNAs (EIciRNAs) based on their composition
FIGURE 2
FIGURE 2
CircRNA‐encoded proteins/peptides in human cancers. CC, colon cancer; GC, gastric cancer; HCC, hepatocellular carcinoma; TNBC, triple‐negative breast cancer
FIGURE 3
FIGURE 3
Mechanism of cap‐independent translation initiated by IRES (eg, circFBXW7 in glioblastoma) and by m6A modification in the 5′‐UTR. eIF4G2, eukaryotic translation initiation factor 4 gamma 2; IRES, internal ribosome entry site; m6A, N6‐methyladenosine; METTL14, methyltransferase‐like 14; METTL3, methyltransferase‐like 3; USP28, ubiquitin‐specific peptidase 28; UTR, untranslated region; YTHDC1, YTH domain‐containing 1; YTHDF1, YTH domain family protein 1; YTHDF3, YTH domain family protein 3
See this image and copyright information in PMC

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