Growing studies have indicated the involvements of long noncoding RNAs (lncRNAs) in the initiation and progression of various tumors. We aimed to investigated the role of lncRNA LMCD1 antisense RNA 1 (LMCD1-AS1) in osteosarcoma development. We found that LMCD1-AS1 and SP1 were highly expressed in osteosarcoma tissues and cell lines. High levels of LMCD1-AS1 were correlated with positively metastasis and poor clinical prognosis. Moreover, we showed that SP1 can bind to the promoter region of LMCD1-AS1, resulting in its overexpression in osteosarcoma. Functionally, silencing of LMCD1-AS1 suppressed the proliferation, migration, invasion and EMT progress of osteosarcoma cells. Mechanistic studies revealed that LMCD1-AS1 was a sponge of miR-106b-5p activity. LMCD1-AS1 modulated survival of osteosarcoma via targeting miR-106b-5p. Overall, we firstly indicated that LMCD1-AS1 overexpression contributes to osteosarcoma development and poor clinical outcome, suggesting that LMCD1-AS1 may be a novel diagnostic and prognostic biomarker for osteosarcoma and a target for osteosarcoma therapy. (C) 2020 Elsevier Inc. All rights reserved.