Long noncoding RNAs (IncRNAs) are recognized as a class of critical regulators in various tumors. Recently, IncRNA LSINCT5 has been reported to promote the progression of bladder cancer, ovarian cancer, gastric cancer, and breast cancer. However, the biological function of LSINCT5 remains elusive in osteosarcoma (OS). In our study, we found that LSINCT5 was significantly upregulated in OS tissues than in adjacent normal tissues. Additionally, the expression of LSINCT5 was inversely associated with the prognosis of patients with OS. LSINCT5 knockdown dramatically inhibited OS cell proliferation in vitro and tumor growth in vivo. Mechanistic exploration revealed that LSINCT5 interacted with EZH2 to suppress the expression of APC, a negative regulator of the Wnt/beta-catenin pathway. Moreover, rescue assays suggested that LSINCT5 exerted oncogenic roles by partially inhibiting APC expression in OS. In summary, our study demonstrated that LSINCT5 was a promising candidate for OS prognosis and therapy. (C) 2018 Elsevier Inc. All rights reserved.