SP1-induced lncRNA LINC00689 overexpression contributes to osteosarcoma progression via the miR-655/SOX18 axis.

OBJECTIVE: Many findings have demonstrated long noncoding RNAs (lncRNAs) as crucial regulatory molecules in the progression of osteosarcoma. The aim of this study was to explore the roles and mechanisms of LncRNA LINC00689 (LINC00689) in osteosarcoma. PATIENTS AND METHODS: Differential levels of LINC00689 and miR-655 in osteosarcoma samples and cell lines were analyzed by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR). The associations between LINC00689 expression and prognostic significance of osteosarcoma patients were analyzed using a series of statistical assays. Loss-of-function and gain-of-function assays were performed to investigate the role of LINC00689 in proliferation and metastasis in vitro. Bioinformatic assays, Luciferase report assays, and rescue assays were applied to illustrate the ceRNA mechanism network of LINC00689/miR-655/SOX18. RESULTS: We found that LINC00689 expression was distinctly upregulated in osteosarcoma specimens and cell lines. MiR-655 displayed a trend of remarkably decreased expression in osteosarcoma tissues. In addition, we showed that LINC00689 could specifically interact with the promoter of SP1 and activate LINC00689 transcription. Further clinical studies indicated that higher levels of LINC00689 were associated with advanced clinical stage, positively distant metastasis, and unfavorable clinical outcome. Functional studies revealed that the knockdown of LINC00689 suppressed the proliferation, migration, and invasion of osteosarcoma cells, and promoted apoptosis. Final mechanistic investigations confirmed that upregulation of LINC00689 competitively bound to miR-655 that prevented SOX18 from miRNA-mediated degradation, thus facilitating osteosarcoma progression. CONCLUSIONS: All our findings suggested that SP1-induced upregulation of LINC00689 promoted osteosarcoma progression by regulating miR-655/ SOX18 axis, which provided a novel insight for osteosarcoma tumorigenesis.