Interleukin 1β/1RA axis in colorectal cancer regulates tumor invasion, proliferation and apoptosis via autophagy

Interleukin (IL)-1β is a member of the IL-1 family of proteins. IL-1 receptor antagonist (IL-1RA) is an agent that binds to the IL-1 receptor, preventing IL-1 from transmitting signals to cells. The present study aimed to identify the role of the IL-1β/1RA axis in epithelial-mesenchymal transition (EMT), cell invasion, migration, proliferation and clone formation in colorectal cancer (CRC) and to determine its underlying mechanisms of action. Significantly increased expression of both IL-1β and IL-1RA was identified in CRC patient data uploaded in The Cancer Genome Atlas database, and in tumor tissues when compared with matched control tissue. High expression of IL-1β was associated with an increased rate of overall survival and recurrence-free survival. Further research revealed that the IL-1β gene was co-expressed with the IL-1RA gene in tumors of CRC patients. It was additionally determined that recombinant human (rh)IL-1β suppressed autophagy as well as EMT in HCT-116 cells compared with control-treated cells, whereas rhIL-1RA exhibited the opposite effect. In addition, autophagy activator rapamycin (RAPA) rescued the inhibition of EMT in rhIL-1β-treated HCT-116 cells. Moreover, rhIL-1β inhibited cell invasion, migration, proliferation and colony-formation ability, when compared with a control treatment. Compared with a control treatment rhIL-1RA promoted cell invasion, migration, proliferation, but had no effect on clone formation ability. Furthermore, both rhIL-1RA and RAPA rescued inhibition of cell invasion, migration and clone formation ability in rhIL-1β-treated HCT-116 cells. RAPA, but not rhIL-1RA, rescue inhibited proliferation in rhIL-1β-treated HCT-116 cells compared with controls. In addition, it was confirmed that rhIL-1β inhibited the growth of subcutaneous xenografts in nude mice, when compared with control treatments. These results indicated that upregulation of the IL-1β/1RA axis in CRC regulated EMT, cell invasion and migration, proliferation and clone formation via autophagy.