Abstract
Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Due to the lack of typical symptoms and difficulties in early diagnosis, PAAD has a high mortality rate. Therefore, it is essential to identify novel specific biomarkers for the application of targeted therapies. A previous study suggested that agmatinase (AGMAT) may fulfill important roles in tumor progression; however, these roles and the underlying mechanisms of AGMAT involvement in PAAD have yet to be thoroughly investigated. To address this shortcoming, in the present study the expression and prognostic significance of AGMAT were analyzed via several bioinformatics databases. Gain- and loss-of-function experiments were subsequently performed to observe the impact of AGMAT on the proliferation and metastasis of PAAD cells via Cell Counting Kit 8 (CCK-8) assay, colony formation assay, and cell migration and invasion assays in vitro. In order to probe the mechanisms involved, western blot assays were performed. AGMAT was found to be overexpressed in PAAD, and it was positively associated with a poor prognosis. Stable overexpression of AGMAT was found to lead to a marked increase in cell proliferation and metastasis through activation of the transforming growth factor-β (TGFβ)/Smad pathway, and via enhancing epithelial-mesenchymal transition (EMT). In conclusion, the results of the present study suggest that AGMAT may be an oncogene, and a pivotal mechanism has been uncovered in which AGMAT facilitates the progression of PAAD tumorigenesis through the TGFβ/Smad pathway.