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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.
Oncology Reports – Spandidos Publications
Published: Mar 1, 2020
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