Knockdown of lncRNA FEZF1-AS1 Inhibits metastasis of Osteosarcoma Cells by miR-4456/GALNT10

Abstract

Background: Osteosarcoma (OS) is among the malignant tumors with high mortality and low survival, especially in children and adolescents. Research shows that LncRNA FEZ family zinc finger 1 antisense RNA 1 (FEZF1-AS1) enhances osteosarcoma progression. Nevertheless, the function and mechanism of FEZF1-AS1 in metastasis of OS remains unclear.Methods: We used qRT-PCR to assay for the expression of FEZF1-AS1, miR-4456, and GALNT10 in OS tissue specimens and cell lines. We also investigated the progression of OS through metastasis using the wound healing and Transwell assays. Moreover, we used the dual-luciferase reporter test, RIP assays, and western blot to validate whether FEZF1-AS1 serves as a competing endogenous RNA (ceRNA), modulating the expression of GALNT10 through sponging miR-4456 in OS.Results: FEZF1-AS1 was up modulated in OS tissues. Silencing FEZF1-AS1 repressed OS cell migration and invasion. microRNA-4456 (miR-4456) was involved in FEZF1-AS1-induced migration and invasion. miR-4456 was down modulated in OS tissue specimens and cell lines. Functionally, the up modulation of miR-4456 reversed the facilitative influence of FEZF1-AS1 on OS cell infiltration and migration. Mechanically, FEZF1-AS1 interacted with miR-4456 in a reciprocal suppressed manner. Moreover, miR-4456 targets GALNT10 via the Luciferase assay. Besides, the up modulation of GALNT10 reversed the migration and invasion inhibited by FEZF1-AS1 knockdown. Silencing of FEZF1-AS1 inhibits OS cell infiltration and migration through miR-4456 /GALNT10 sponging.Conclusion: Herein, we demonstrated that FEZF1-AS1 is a prospective bio signature of metastasis in OS patients. Mechanistically, we showed that the FEZF1-AS1/miR-4456/GALNT10 axis is a target for novel therapeutic development for OS.