The oncogenic role of REG γ is exerted by activating the Wnt/β-catenin signaling pathway in osteosarcoma

摘要

Background: Proteasome activator γ (REG γ) expression was found to be upregulated and to play critical roles in several cancers. However, the effect of REG γ on osteosarcoma (OS) remains unclear. The objective of the present study was to explore the clinical significance of REG γ and its function in regulating the progression of OS. Methods: Quantitative reverse transcription-polymerase chain reaction (qRT-PCR), western blotting (WB) and immunohistochemistry (IHC) analyses were performed to detect the expression levels of REG γ in OS tissues and cell lines. Then, the effects of REG γ expression on OS cell behavior in vitro were analyzed by Cell Counting Kit-8 (CCK-8), ethylene deoxyuridine (EdU), colony formation, flow cytometry, wound healing and transwell assays. The protein and mRNA levels of components involved in the Wnt/β-catenin pathway were evaluated using WB and qRT-PCR, respectively. Results: We found that REG γ expression was significantly upregulated in both OS tissues and cell lines. Our in vitro assay results confirmed that knockdown of REG γ inhibited cell proliferation, migration, and invasion and induced apoptosis and cell cycle arrest in OS. Additionally, through WB and qRT-PCR analyses, we found that REG γ depletion markedly decreased the β-catenin, cyclin D1 and c-myc expression levels and increased the GSK-3β expression levels in OS cell lines. Conclusions: Our results revealed that REG γ plays an oncogenic role in OS by activating the Wnt/β-catenin pathway, indicating that REG γ may be a promising therapeutic target for OS patients.