lncRNA FBXL19-AS1 regulates osteosarcoma cell proliferation, migration and invasion by sponging miR-346.

ONCOTARGETS AND THERAPY(2018)

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摘要
Background: It was recently reported that Inc RNA FBXL19 antisense RNA 1 (FBXL19-AS1) is a novel tumor-promoting RNA that contributes to tumor progression by sponging miRNAs. However, the expression and function of FBXL19-AS1 in osteosarcoma (OS) have not been investigated. Methods: Cell proliferation was assessed by the CCK-8 and colony formation assays, while cell migration and invasion were assessed using wound healing and transwell invasion assays, respectively. Quantitative reverse transcriptase PCR and immunolluorescence were used to detect the level and subcellular localization of FBXL19-AS1 expression. Interactions between miRNAs and FBXL19-AS1 were determined using luciferase reporter assays. Finally, in vivo experiments were performed to assess tumor formation. Results: We first showed that IncRNA FBXL19-AS1 was upregulated in OS tissues and cell lines. In vitro experiments showed that FBXL19-AS1 promoted OS cell proliferation, migration, and invasion. Inhibiting miR-346 led to a significant upregulation of FBXL19-AS1, suggesting FBXL19-AS1 was negatively regulated by miR-346, which was further confirmed by the inverse correlation between FBXLI9-AS1 and miR-346 expression in OS patient specimens. Furthermore, we proved that miR-346 could directly target FBXL19-AS1 through luciferase assays, suggesting FBXL19-AS1 could sponge miR-346. Additionally, inhibiting miR-346 blocked the effects of silencing FBXL19-ASI on proliferation, migration, and invasion. Moreover, inhibiting FBXL19-ASI significantly promoted the malignancy of MG63 and 143B cells in vivo. Conclusion: We validated FBXL19-AS1 as a novel oncogenic IncRNA and demonstrated the molecular mechanism through which it promotes OS progression. This work advances our understanding of the clinical significance of this RNA species.
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关键词
FBXL19-AS1,miR-346,proliferation,competing endogenous RNA,osteosarcoma,IncRNA,miRNA,ceRNA,cancer
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