INSIG1 and colorectal carcinoma: Since the ubiquitin-proteasome and autophagy-lysosome pathways are two major systems for protein clearance in eukaryotic cells [18], we treated CRC cells with the proteasome inhibitor MG132 or autophagic-sequestration inhibitor 3-methyladenine (3-MA) to further investigate the molecular mechanisms underlying circINSIG1-121-mediated INSIG1 degradation.