Table 2.

CircRNAs in digestive system cancer: signaling pathway and function

circRNA	Cancer type	Expression in tumors	Pathway/regulatory network	Function/clinical association	Ref.
cir-ITCH	ESCC	Low	cir-ITCH-miR-7/miR-17/miR-214-ITCH-Wnt signaling	Reduces cell viability and arrests proliferation in ESCC cells	[67]
	Colorectal cancer	Low	cir-ITCH-Wnt signaling	Plays an anti-tumor role	[78]
	HCC	Low	Not mentioned	Has an inhibitory effect on HCC, and associates with survival of HCC	[112]
hsa_circ_006793	ESCC	High	Not mentioned	Correlates with tumor differentiation and TNM stage; promotes proliferation and migration of ESCC cell	[68]
circPVT1	Gastric cancer	High	circPVT1-miR-125-E2F2	An independent prognostic factors for overall survival and disease free survival in patients with gastric cancer; affects proliferation of gastric cancer cells	[24]
ciRS-7 (CDR1as)	Gastric cancer	High	ciRS-7-miR-7-PTEN/PI3K/AKT pathway	An independent risk factor of overall survival; Correlates with a more aggressive oncogenic phenotype	[73]
	Colorectal cancer	High	ciRS-7-miR-7-EGFR/RAF1/MAPK pathway	An independent risk factor for overall survival with tumor stimulative effect	[79]
	HCC	high	ciRS-7-miR-7-EGFR or PI3K/AKT/mTOR pathway	An independent risk factor of hepatic microvascular invasion; correlates with the proliferation of hepatocellular carcinoma cells and the deterioration of HCC	[83,84]
hsa_circ_0001895	Gastric cancer	Low	Not mentioned	Associates with cell differentiation, Borrmann type, and tissue CEA expression; has a better sensitivity and specificity than the commonly used biomarkers of gastric cancer	[74]
circLARP4	Gastric cancer	Low	circLARP4-miR-424-LATS1-YAP pathway	An independent prognostic marker for overall survival of gastric cancer patients as well as the patients with chemotherapy; inhibits DNA synthesis, cell proliferation and invasion; correlates with tumor size and lymphatic metastasis	[75]
hsa_circ_0000745	Gastric cancer	Low	hsa_circ_0000745-miRNAs	Associates with tumor differentiation; has higher sensitivity and specificity than serum CEA levels	[76]
hsa_circ_000984	Colorectal cancer	High	hsa_circ_000984-miR-106b-CDK6	Promotes colorectal cancer cell proliferation, migration, invasion and tumor formation; correlates with advanced colorectal cancer	[81]
hsa_circ_001569	Colorectal cancer	High	hsa_circ_001569-miR-145-E2F5/BAG4/FMNL2	Promotes colorectal cancer cell proliferation and invasion	[82]
circCCDC66	Colorectal cancer	High	circCCDC66-miRNAs-oncogenes	Promotes colorectal cancer cell proliferation, migration, invasion, and anchorage-independent growth; associates with poor prognosis	[22]
circHIPK3	Colorectal cancer	High	c-Myb-circHIPK3-miR-7-FAK, IGF1R, EGFR, YY1	Positively correlated with metastasis and advanced clinical stage; an independent prognostic factor of poor overall survival in colorectal cancer	[80]
circMTO1	HCC	Low	circMTO1-miR-9-p21	Suppresses hepatocellular carcinoma cell proliferation and invasion; associates with survival of HCC	[26]
hsa_circ_0004018	HCC	Low	hsa_circ_0004018-miR-30e-5p/miR-626-MYC	Correlates with serum AFP level, tumor diameters, differentiation, BCLC stage and TNM stage; HCC-stage-specific expression features in diverse chronic liver diseases	[85]
circZKSCAN1	HCC	Low	circZKSCAN1-miRNA-Mrna	Associates with tumor numbers, cirrhosis, vascular invasion, or microscopic vascular invasion; inhibits growth, migration, and invasion of HCC	[86]
cSMARCA5	HCC	Low	cSMARCA5-miR-17-3p/miR-181b-5p-TIMP3	An independent risk factor for overall survival and relapse-free survival after hepatectomy; inhibits the proliferation and migration of hepatocellular carcinoma cells	[87]
circRNA_100338	HCC	High	circRNA_100338-miR-141-3p	Correlates with a low cumulative survival rate and metastatic progression in HCC patients with hepatitis B	[88]
circARSP91	HCC	Low	AR-ADAR1-CircARSP91	Suppresses tumor growth	[89]