Abstract
circular RNA (circRNA) is a closed ring structure formed by cyclic covalent bonds connecting the 5’-end and 3’-end of pre-mRNA. circRNA is widely distributed in eukaryotic cells. Recent studies have shown that circRNA is involved in the pathogenesis and development of multiple types of diseases, including tumors. circRNA is specifically expressed in tissues. And the stability of circRNA is higher than that of linear RNA, which can play biological roles through sponge adsorption of miRNA, interaction with RNA binding protein, regulation of gene transcription, the mRNA and protein translation brake, and translation of protein and peptides. These characteristics render circRNAs as biomarkers and therapeutic targets of tumors. Gastrointestinal tumors are common malignancies worldwide, which seriously threaten human health. In this review, we summarize the generation and biological characteristics of circRNA, molecular regulation mechanism and related effects of circRNA in gastrointestinal tumors.
Highlights
Gastrointestinal tumors such as gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma and gallbladder cancer are common malignancies worldwide, which seriously threaten human health
We summarize the generation and biological characteristics of circular RNA (circRNA), molecular regulation mechanism and related effects of circRNA in gastrointestinal tumors
In 1976, Sanger et al found that the pathogenic plant virus was a single-stranded covalently closed circRNA molecule, but scientists considered that it was connected by host cell enzymes rather than formed by reverse splicing [5]. circRNA formed by reverse splicing was first reported in the 1890s [6,7,8,9]
Summary
Gastrointestinal tumors such as gastric cancer, esophageal cancer, colorectal cancer, pancreatic cancer, hepatocellular carcinoma and gallbladder cancer are common malignancies worldwide, which seriously threaten human health. The formation modes of circRNA include intronic complementary sequence (ICS) pair-driven cyclization, RNA binding protein (RBP)-driven cyclization and lariat-driven cyclization [17]. Quaking binds to ICS to make the splice site closer to facilitate reverse splicing to increase circRNAs formation [22]. In the exon skipping event, the exon lariat formed by the covalently combined splice acceptor and splice donor provided by the exon is another formation of circRNA (Figure 2E) [23]. The formation of intron lariat caused by intron removal during the pre-mRNA splicing process can give rise to circRNA (Figure 2F) [12]. The high transcription elongation rate renders transcription of more downstream genes and increases ICS matching that skipps exon, reverse splicing is more likely to form circRNA [10]. When the canonical splicing speed becomes slow or the splicing complex is consumed, the level of circRNA would increase, which is associated with the transformation from canonical splicing to reverse splicing [25]
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