lncRNA FBXL19-AS1 regulates osteosarcoma cell proliferation, migration and invasion by sponging miR-346
Authors Pan RS, He ZX, Ruan WY, Li S, Chen H, Chen ZY, Liu F, Tian XB, Nie YJ
Received 28 December 2017
Accepted for publication 17 July 2018
Published 29 November 2018 Volume 2018:11 Pages 8409—8420
Checked for plagiarism Yes
Review by Single-blind
Peer reviewer comments 3
Editor who approved publication: Prof. Dr. Geoffrey Pietersz
Runsang Pan,1,2 Zhixu He,2 Wanyuan Ruan,2 Sun Li,1,3 Hui Chen,1,3 Zhiyu Chen,1,3 Fang Liu,1 Xiaobin Tian,1,3 Yingjie Nie1,3
1Department of Clinical Medicine, Guizhou University, Guiyang, Guizhou Province, China; 2Department of Orthopedics, Guiyang Children’s Hospital, Guiyang, Guizhou Province, China; 3Department of Orthopedics, Guizhou Provincial People’s Hospital, Guiyang, Guizhou Province, China
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.
Keywords: FBXL19-AS1, miR-346, proliferation, competing endogenous RNA, osteosarcoma, lncRNA, miRNA, ceRNA, cancer