OBJECTIVE: Osteosarcoma (OS) is a kind of malignant bone tumor. The aim of the manuscript is to investigate the clinical significance and the functional effects of long non-coding (lncRNA) colon cancer-associated transcript 2 (CCAT2) in osteosarcoma. PATIENTS AND METHODS: Expression of CCAT2 was detected by quantitative Real-time PCR (qRT-PCR) in 50 cases of osteosarcoma tissue samples and adjacent normal bone tissues. Kaplan-Meier survival analysis and log-rank test were used to assess the association between CCAT2 expression and prognosis of OS patients. Cell Counting Kit 8 and cell colony formation assays were performed to evaluate cell proliferation. The protein expression of PCNA, p-GSK3 beta, GSK3 beta, and beta-catenin were analyzed using Western blot analysis. RESULTS: We demonstrated that lncRNA CCAT2 expression was significantly upregulated in OS tissues compared to adjacent normal bone tissues. Higher lncRNA CCAT2 expression positively associated with larger tumor size, advanced tumor stage and poor overall survival (OS) rate of patients. In vitro, knock-down of lncRNA CCAT2 suppressed cell proliferation and colony formation ability. In contrast, overexpression of lncRNA CCAT2 showed promoting cell proliferation effects in OS. Also, we found that knockdown of lncRNA CCAT2 inhibited GSK3 beta/beta-catenin signaling by reducing p-GSK3 beta and beta-catenin expression, but increasing GSK3 beta expression. CONCLUSIONS: Our results showed that CCAT2 is a crucial oncogene in OS and may be a potential therapeutic target of OS.