PDCD5 inhibits osteosarcoma cell metastasis via targeting TGF-β1/Smad signaling pathway and is associated with good prognosis

Whether programmed cell death 5 (PDCD5) is effective for tumor metastasis remains unclear. In this study, the expression of PDCD5 in 63 osteosarcoma (OS) tissues and two OS cell lines was analyzed. Then the relationship between PDCD5 expression and clinicopathological features of OS was studied. In addition, adhesion, wound healing, Transwell and Matrigel tube formation assays were used to explore the role of PDCD5 in OS cell adhesion, migration, invasion and angiogenesis. Western blotting was used to detect the protein expression of TGF-beta 1/Smad signaling pathway and epithelial-mesenchymal transition (EMT)-related markers. At the same time, key molecules involved in migration, invasion and EMT in tumor specimens were assessed by immunohistochemistry. The data showed that PDCD5 overexpression significantly attenuated OS cell adhesion, migration, invasion and angiogenesis. Furthermore, PDCD5 knockdown caused an opposite effect on these phenotypes in vitro. PDCD5 inhibited tumor metastasis by attenuating EMT in OS cells. PDCD5 knockdown enhanced the incidence of metastasis and EMT in OS cells. Furthermore, PDCD5 expression was reduced by transforming growth factor-beta 1 (TGF-(beta 1) in a time-dependent manner, and TGE-beta 1-induced EMT was induced by PDCD5 knockdown. Inactivation of the TGF-beta 1/ Smad signaling pathway was involved in the anti-tumor function of PDCD5 in OS. Furthermore, tumor progression in OS patients was associated with low expression of PDCD5, indicating a decrease in survival and a poor prognosis. Our results suggest that PDCD5 may attenuate EMT by inhibiting TGF beta 1/Smad signaling pathway to inhibit OS metastasis and may be a potential adjuvant genetic therapy for OS.