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Review
. 2022 Jun 7;10(1):41.
doi: 10.1186/s40364-022-00388-y.

Current advances and future perspectives on the functional roles and clinical implications of circular RNAs in esophageal squamous cell carcinoma: more influential than expected

Chenxi Ju #  1 , Jing He #  2 , Chang Wang #  1 , Jinxiu Sheng  1 , Jinlin Jia  1 , Dan Du  1 , Hongle Li  3 , Mingxia Zhou  4 , Fucheng He  5
Affiliations
Review

Current advances and future perspectives on the functional roles and clinical implications of circular RNAs in esophageal squamous cell carcinoma: more influential than expected

Chenxi Ju et al. Biomark Res. .

Abstract

Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive gastrointestinal cancers with high incidence and mortality. Therefore, it is necessary to identify novel sensitive and specific biomarkers for ESCC detection and treatment. Circular RNAs (circRNAs) are a type of noncoding RNAs featured by their covalently closed circular structure. This special structure makes circRNAs more stable in mammalian cells, coupled with their great abundance and tissue specificity, suggesting circRNAs may present enormous potential to be explored as valuable prognostic and diagnostic biomarkers for tumor. Mounting studies verified the critical roles of circRNAs in regulating ESCC cells malignant behaviors. Here, we summarized the current progresses in a handful of aberrantly expressed circRNAs, and elucidated their biological function and clinical significance in ESCC, and introduced a series of databases for circRNA research. With the improved advancement in high-throughput sequencing and bioinformatics technique, new frontiers of circRNAs will pave the path for the development of precision treatment in ESCC.

Keywords: Diagnosis; Esophageal squamous carcinoma (ESCC); Treatment; circRNA.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
Biogenesis of circRNAs. A lariat-driven circularization: the folding of pre-mRNA caused it to form lariat structure which are generated from the link of 5’ splice acceptor and 3’ splice donor. Furthermore, the lariat structure conduct internal splicing of introns to form EIciRNA or EcRNA; B intron-pairing-driven circularization: pre-mRNA contained abundant complementary sequence in introns flanking the exons can connect to form EIciRNA or EcRNA by base pairing; C RBPs driven circularization: intronic motifs flanking exons have RBPs binding sites which can interact with RBPs and induce circularization, in this process, EIciRNA or EcRNA can be produced; D intron cyclization: pre-mRNA conduct internal splicing to remove introns and generate mature mRNA. Some spliced introns can circularization to form ciRNA; E the formation of tricRNAs: induced by tRNA splicing endonuclease (TSEN) which can recognize bulge-helix-bulge (BHB) motif, pre-tRNA can undergo internal splicing to generate tricRNA and tRNA
Fig. 2
Fig. 2
Function of circRNAs. A EIciRNA and EcRNA can interact with U1 snRNP to regulate host gene transcription in nucleus; In cytoplasm, (B) circRNAs act as miRNA sponge to reduce the function of miRNA; C circRNAs can bind and sequester proteins; D circRNAs can be translated into polypeptide
Fig. 3
Fig. 3
Summary of the function of circRNAs in ESCC. CircRNAs can participate in the origin and development of ESCC, including cell proliferation, cell death, migration and therapy resistance
Fig. 4
Fig. 4
Summary of knockdown and overexpression strategies for circRNAs. Several therapeutic strategies based on the manipulation of circRNAs expression is expected to provide a brighter prospect for cancer therapy
See this image and copyright information in PMC

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