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Review
. 2020 Aug 11:26:e923832.
doi: 10.12659/MSM.923832.

Current Status of Research on the Role of Circular RNAs in Hepatocellular Carcinoma and Clinical Implications

Ren-Chao Zou  1 , Ling-Lin Li  2   3 , Hong-Ling Yuan  2
Affiliations
Review

Current Status of Research on the Role of Circular RNAs in Hepatocellular Carcinoma and Clinical Implications

Ren-Chao Zou et al. Med Sci Monit. .

Abstract

The latest statistics show that rates of morbidity and mortality for hepatocellular carcinoma are gradually increasing over time. Accumulating evidence indicates that circular RNAs (circRNAs) participate in the regulation of gene transcription and translation and exert a crucial role in endogenous RNA network. circRNAs are implicated in the pathogenesis of numerous tumors including hepatocellular carcinoma (HCC), gastric carcinoma and bladder cancer. Of note, the effect of circRNAs in HCC has drawn increasing public attention. Previous studies revealed that the function of circRNAs mainly consists of sponges of miRNA and RNA-binding proteins, alternative splicing of pre-mRNAs, transcriptional and translational regulators, and potential to encode proteins. In addition, recent research data indicate that the expression level of circRNAs is closely correlated with metastasis, invasion, and occurrence of HCC in patients. These findings imply that circRNAs may be useful as biomarkers for diagnosis and prediction of prognosis of HCC. In this review, we have systemically summarized current viewpoints regarding the role of circRNAs expression in HCC to provide an important reference illustrating the underlying mechanism of HCC.

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Figures

Figure 1
Figure 1
Biogenesis of circular RNAs [23]. (A) Lariat-driven circularization. The 3′ hydroxyl of the upstream exon reacts with the 5′ phosphate of the downstream exon to form a covalent linkage, then producing a lariat including exons and introns. The 2′ hydroxyl of the 5′ intron interacts with the 5′ phosphate of the 3′-intron to form an ecircRNA following an interaction between the 3′ hydroxyl of the 3′ exon and the 5′ phosphate of the 5′ exon. (B) RNA-binding protein (RBP)-driven circularization. RBPs accelerate interaction of the downstream intron and upstream intron, thereby promoting formation of ecircRNA. (C) Base-pairing-driven circularization. The downstream introns and upstream introns are paired depends on inverse-repeating/complementary sequences. Formation of ecircRNA/EIciRNA was derived from the introns are removed/retained. (D) Biosynthesis of ciRNA. Formation of ciRNAs mainly based on a 7-nt GU-rich element and an 11-nt C-rich element to escape debranching and exonucleolytic degradation. (E) Formation of tricRNA. tRNA splicing enzymes divide pre-tRNA into two parts: TricRNAs are generated by a 3′–5′ phosphodiester bond and the other part generates tRNAs.
Figure 2
Figure 2
The function of circRNAs in HCC carcinogenesis. This graph demonstrates the role of circRNAs in HCC carcinogenesis, including positive and negative effects, respectively.
See this image and copyright information in PMC

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