Novel potential tumor biomarkers: Circular RNAs and exosomal circular RNAs in gastrointestinal malignancies

Abstract

Background: Circular RNAs (circRNAs) are structural ubiquitous RNA molecules. Accumulating evidences have elucidated that circRNAs play essential roles in the pathogenesis of diseases including cancers. Exosomal circRNAs are those circRNAs stably existing in exosomes and having high clinical values as novel potential diagnostic biomarkers of many diseases. Gastrointestinal (GI) malignancies, including pancreatic cancer, colorectal cancer, hepatocellular carcinoma (HCC), and gastric cancer, are leading causes of mortality worldwide and a major global health burden. However, no ideal tumor biomarkers of screening early GI cancers are currently available.

Methods: We collected data through Web of Science. The search terms used were as follows: circular RNA, circRNA, exosomes, exosomal circRNAs, biomarkers, gastrointestinal malignancies, pancreatic cancer, hepatocellular carcinoma, HCC, gastric cancer, colorectal cancer, physiological functions, biogenesis, molecular mechanism. Only articles published in English were included.

Results: We found that several circRNAs and exosomal circRNAs have been used as potential biomarkers to screen GI cancers including pancreatic cancer (hsa_circ_0001649, circ_0007534, circ_0030235, circRHOT1, circZMYM2, circ-LDLRAD3, chr14:101402109-101464448C, chr4:52729603-52780244C, circ-IARS, and circ-PDE8A), HCC (circSETD3, circADAMTS13, hsa_circ_0007874, hsa_circ_104135, circFBLIM1, cSMARCA5, circRNA-100338, and circPTGR1), colorectal cancer (hsa_circ_0001178, hsa_circ_0000826, hsa_circ_0004771, circDDX17, circITGA7, and circHIPK3), and gastric cancer (hsa_circ_0074362, circNRIP1, circAKT3, circ-DONSON, circPSMC3, circ-KIAA1244, circPVRL3, circPVT1, hsa_circ_0000096, ciRS-133, hsa_circ_0001017, and hsa_circ_0061276).

Conclusion: CircRNAs and exosomal circRNAs have the potential high clinical diagnostic values for GI malignancies.

Keywords: biomarkers; circular RNAs; exosome; gastrointestinal malignancies; non-invasive diagnosis.

FIGURE 1

Gastrointestinal cancer‐associated circular RNAs

FIGURE 2

CircRNAs and exosomal circRNAs used as biomarkers. In the nuclei of cancer cells, circRNAs are produced by pre‐mRNA after transcription. The formation of circRNAs may involve one exon, several exons, several introns, or only one intron. CircRNAs may be released into the blood directly or with exosomes