Long noncoding RNA PVT1 promotes metastasis via miR-484 sponging in osteosarcoma cells

M. Yan, X.-F. Pan, Y. Liu, S. Zhao, W.-Q. Gong, W. Liu

Department of Spinal Surgery, The First Hospital of Jilin University, Changchun, P.R. China. lwspineac@163.com

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• Oncology

OBJECTIVE: Long noncoding RNAs (lncRNAs) are widely involved in various malignancies including osteosarcoma. In the current study, we aimed to illustrate the role of lncRNA plasmacytoma variant translocation 1 (PVT1) in osteosarcoma.

PATIENTS AND METHODS: Expression of PVT1 and microRNA-486 (miR-486) in osteosarcoma tissue specimens and cell lines were detected by quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) assays and in situ hybridizations (ISH) assay. Transwell migration/invasion assays were performed to determine the metastatic ability changes in osteosarcoma cells. Kaplan-Meier survival analysis was applied to analyze the overall survival (OS) of patients with osteosarcoma. Luciferase assays were used to evaluate the targeted binding effect between PVT1 and miR-486.

RESULTS: We illustrated that lncRNA plasmacytoma variant translocation 1 (PVT1) was upregulated in osteosarcoma, and it was correlated with poor prognosis of patients with osteosarcoma. Furthermore, we found that PVT1, via constructed loss of function and gain of function assays, promoted osteosarcoma cells migration and invasion. Meanwhile, we demonstrated that microRNA-486 (miR-486) was involved in PVT1-induced migration and invasion. We also uncovered that miR-486 was downregulated in osteosarcoma tissue specimens and cell lines. Functionally, we showed that upregulation of miR-486 reversed the facilitative effect of PVT1 on osteosarcoma cells migration and invasion, and vice versa. Mechanically, we illustrated that PVT1 interacted with miR-486 in a reciprocal suppressed manner. Moreover, we found that miR-486 could target to PVT1 via Luciferase assay. Lastly, we proved that PVT1 promoted osteosarcoma cells migration and invasion through miR-486 sponging.

CONCLUSIONS: We demonstrated that PVT1, functioning as an oncogene, promotes osteosarcoma cells metastasis via miR-486 sponging. PVT1/miR-486 axis might be a novel target in the molecular treatment of osteosarcoma.

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