Down-regulation of RAC2 by small interfering RNA restrains the progression of osteosarcoma by suppressing the Wnt signaling pathway

Abstract

Osteosarcoma (OS) is the most common primary malignancy of bone and is characterized by a high malignant and metastatic potential. Microarray-based differentially expressed gene screening determined RAC2 as the candidate gene related to OS. Highly expressed RAC2 and activated Wnt signaling pathway were determined in OS tissues using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and Western blot analysis. The OS cells were transfected with siRNA-RAC2 or treated with BIO (activator of Wnt pathway), whereby the effects of siRNA-RAC2 on cell proliferation, invasion, cycle and apoptosis were analyzed by CCK-8, Transwell assay and flow cytometry. The mRNA and protein levels of RAC2 and the Wnt signaling pathway-, proliferation- and apoptosis-related genes in OS cells were determined by RT-qPCR and Western blot assay. Importantly, siRNA-mediated RAC2 silencing inhibited the activation of the Wnt signaling pathway in OS. siRNA-RAC2 inhibited the proliferation and invasion, while impeded OS cell cycle progression and facilitated cell apoptosis. However, activation of Wnt signaling pathway reversed the effects of siRNA-RAC2. Finally, orthotopic xenograft OS mouse model confirmed the in vivo anti-tumor effects by silencing RAC2. Taken together, RAC2 gene silencing could suppress OS progression. The mechanism was obtained by inhibiting the activation of the Wnt signaling pathway.