The oncogenic role of REG gamma is exerted by activating the Wnt/beta-catenin signaling pathway in osteosarcoma.

Background: Proteasome activator gamma (REG gamma) expression was found to be upregulated and to play critical roles in several cancers. However, the effect of REG y on osteosarcoma (OS) remains unclear. The objective of the present study was to explore the clinical significance of REG gamma 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 gamma in OS tissues and cell lines. Then, the effects of REG gamma 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/beta-catenin pathway were evaluated using WB and qRT-PCR, respectively. Results: We found that REG gamma expression was significantly upregulated in both OS tissues and cell lines. Our in vitro assay results confirmed that knockdown of REG gamma 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 gamma depletion markedly decreased the beta-catenin, cyclin D1 and c-myc expression levels and increased the GSK-3 beta expression levels in OS cell lines. Conclusions: Our results revealed that REG y plays an oncogenic role in OS by activating the Wnt/beta-catenin pathway, indicating that REG gamma may be a promising therapeutic target for OS patients.