Abstract
Background
It was recently reported that lncRNA 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 immunofluorescence 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 lncRNA 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 FBXL19-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-AS1 on proliferation, migration, and invasion. Moreover, inhibiting FBXL19-AS1 significantly promoted the malignancy of MG63 and 143B cells in vivo.
Conclusion
We validated FBXL19-AS1 as a novel oncogenic lncRNA and demonstrated the molecular mechanism through which it promotes OS progression. This work advances our understanding of the clinical significance of this RNA species.
Acknowledgments
This study was supported by research funding from National Natural Science Foundation of China (81560269), Guizhou Provincial Department of Science and Technology, J (2015) 2003, G (2014) 7020, Guizhou Provincial People’s Club Hall, (2013) 05, and the Doctor’s Funding from Guizhou Provincial People’s Hospital GZSYBS (2015) 10. We thank James P Mahaffey, PhD, from Liwen Bianji, Edanz Editing China (www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
Disclosure
The authors report no conflicts of interest in this work.