Consistent with these observations, other low-expressed circRNAs act as tumor suppressor genes, such as circMTO1 and circHIAT1 in HCC, circITGA7 and hsa_circ_0000523 in CRC, circPSMC3 and circ_0027599 in GC, hsa_circ_0001649 and hsa_circ_001653 in pancreatic cancer, circ-Foxo3 and cir-ITCH in esophageal cancer, and circMAN2B2 and hsa_circ_0056836 in HCC also showed similar characteristics when their expression levels were restored41,42,56,67,126,135–142. This evidence concerns the gene FOXO3 and hepatocellular carcinoma.