Cancer Management and Research (May 2020)
SP1-Induced Upregulation of lncRNA LINC00514 Promotes Tumor Proliferation and Metastasis in Osteosarcoma by Regulating miR-708
Abstract
Li-Dong Mi, Chuan-Xiu Sun, Sheng-Wei He, Guang-Yu Du Orthopeadic Surgery, Zuanshiwan Hospital District of the Second Hospital of Dalian Medical University, Dalian, Liaoning 116031, People’s Republic of ChinaCorrespondence: Chuan-Xiu SunOrthopeadic Surgery, Zuanshiwan Hospital District of the Second Hospital of Dalian Medical University, Dalian, Liaoning 116031, People’s Republic of ChinaEmail [email protected]: Growing studies have suggested the dysregulation of long non-coding RNAs (lncRNAs) in several tumors, including osteosarcoma (OS). However, limited studies report metastasis-associated lncRNAs in OS. Our present study aimed to explore the roles of lncRNA LINC00514 (LINC00514) in OS.Materials and Methods: The LINC00514 expression was measured using qPCR assays in OS tissues and cell lines. The clinical significance of LINC00514 expression in OS patients was analyzed using chi-square test, Kaplan–Meier assays and multivariate analysis. The possible effects of LINC00514 in tumor cellular progression were determined using a series of functional assays. The mechanisms of LINC00514 action were explored through bioinformatics, luciferase reporter assays and RT-PCR assays. The mechanisms involved the upregulation of LINC00514 expression in OS were determined using luciferase reporter and chromatin immunoprecipitation (ChIP) assays.Results: We showed that LINC00514 expressions were distinctly upregulated in both OS tissues and cell lines, especially in advanced cases. High levels of LINC0051 were positively correlated with advanced tumor stages, distant metastasis, and reduced survival of patients with OS. Functional experiments indicated that silencing of LINC00514 suppressed the ability of cell growth, colony formation and metastasis, whereas promoted cell apoptosis in vitro. Mechanistic investigation revealed that LINC00514 could directly bind to miR-708 and effectively serve as a ceRNA for miR-708. In addition, LINC00514 was upregulated by the transcription factor SP1.Conclusion: Our findings revealed SP1-induced upregulation of LINC00514 as an oncogene in OS through competitively binding to miR-708, suggesting that there are potential diagnostic and treatment values of LINC00514 in OS.Keywords: LncRNA LINC00514, miR-708, osteosarcoma, prognosis, SP1, metastasis
