Long noncoding RNAs (lncRNAs) play an important role in the proliferation and metastasis of osteosarcoma. Identification of the pathogenesis of osteosarcoma and development of new therapeutic strategies against osteosarcoma are urgently needed. In this study, we evaluated the expression of TUG1 (Taurine Upregulated Gene 1) in osteosarcoma tissues and selected it as our target for further analyses. In vitro, we found that TUG1 was upregulated by FOXM1 (Forkhead Box M1) in osteosarcoma cells. TUG1 accelerated osteosarcoma proliferation, migration, and invasion by competitively sponging miR-219a-5p, leading to upregulation of Phosphatidylinositol-4, 5-Bisphosphate 3-Kinase Catalytic Subunit Alpha and activation of the protein kinase B (AKT) signaling pathway. In addition, the AKT pathway activation promoted TUG1 expression by upregulating the expression of FOXM1, forming a positive feedback loop in osteosarcoma. Furthermore, we designed and synthesized therapeutic locked nucleic acids targeting TUG1. The proliferation of osteosarcoma was significantly repressed. Hence, TUG1 may be a potential biomarker and therapeutic target for osteosarcoma.
Keywords: FOXM1; PIK3CA; TUG1; miR-219a-5p; osteosarcoma.
© 2018 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.