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Review
. 2018 Oct 1;8(10):1919-1932.
eCollection 2018.

The emerging role of circular RNAs in gastric cancer

Peina Shi  1   2 , Jiangnan Wan  1   2 , Haojun Song  2 , Xiaoyun Ding  2
Affiliations
Review

The emerging role of circular RNAs in gastric cancer

Peina Shi et al. Am J Cancer Res. .

Abstract

Gastric cancer (GC) ranks as the fourth most common cancer and the third leading cause of cancer-related death worldwide. Circular RNAs (circRNAs) are a new class of long noncoding RNAs characterized by a single-stranded covalently closed loop structure. Emerging evidence reveals the essential function of circRNAs in the occurrence and development of human diseases. Among these, circRNAs are aberrantly expressed in GC and are involved in the progression of GC. In this review, we briefly summarize the current knowledge of the classification, biogenesis and biological functions of circRNAs, with an emphasis on their relationship with GC. As our understanding of the relation between circRNAs and GC advances, more diagnostic and therapeutic protocols will be developed for the prevention and treatment of GC.

Keywords: RBP sponge; biomarker; circular RNAs; gastric cancer; miRNA sponge.

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Conflict of interest statement

None.

Figures

Figure 1
Figure 1
Possible models of circRNA and mRNA biogenesis. (1) Direct backsplicing. Introns bordering the circularized exons carry out base pairing, which induces the two exons to undergo alternative backsplicing. Introns of the circRNA are removed or retained to form an ecircRNA or eiciRNA. (2) Exon skipping. A downstream exon skips over one or more exons to link an upstream exon, then forms a lariat containing both exons and introns. Introns of the circRNA are removed or retained to form an ecircRNA or eiciRNA. (3) RBP quaking. RBPs bind to recognition elements within introns, then form a bridge between the two flanking intronic sequences, which brings exons in close proximity to undergo backsplicing. Introns of the circRNA are removed or retained to form an ecircRNA or eiciRNA. (4) CiRNA biogenesis. A motif containing an 11 nt C-rich element near the branchpoint and a 7 nt GU-rich element near the 5’ splice escapes the debranching and degradation after the canonical pre-RNA splicing, and forms a ciRNA. (5) Canonical pre-mRNA splicing and mRNA biogenesis.
Figure 2
Figure 2
Putative functions of circRNAs. (1) CircRNAs as miRNA sponges. Some circRNAs can act as miRNA sponges by competing for miRNA binding sites. (2) CircRNAs as protein translators. Some circRNAs containing IRES have the ability to bind with ribosome and translate into proteins and peptides. M6A can act as IRES to translate circRNAs in human cells. (3) Interaction with RBPs. Some circRNAs can bind RBPs to form RNA-protein complexes and act as RBP sponges. (4) Alternative splicing. Some circRNAs can compete with the biogenesis and processing of mRNA in the nucleus. (5) Transcriptional regulation. Some eiciRNAs and ciRNAs can interact with transcription complexes and promote their parental gene transcription in the nucleus.
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