Long non-coding RNA PGM5-AS1 modulates epithelial-mesenchymal transition and invasion and metastasis of osteosarcoma cells by impairing miR-140-5p-mediated FBN1 inhibition

Abstract

Background Osteosarcoma represents a uncommon tumor occurring in bone possessing elevated rate of incidence and reduced rate of healing. Hence, developing effective therapeutic modalities to treat osteosarcoma is essential. Various long non-coding RNAs (lncRNAs) are engaged in prognostic and diagnostic processes of diseases. Thus, we identified the molecular mechanism of lncRNA PGM5-AS1 in progression of osteosarcoma.Methods Microarray-based analysis was employed to screen the osteosarcoma-related differentially expressed lncRNA. PGM5-AS1 level in osteosarcoma tissues and cells as well as the levels of microRNA-140-5p (miR-140-5p) and fibrillin-1 (FBN1) in osteosarcoma tissues were determined. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were done to find out the relation among PGM5-AS1, miR-140-5p, and FBN1. shRNA, mimic, or inhibitor was applied to alter the levels of PGM5-AS1, miR-140-5p, and FBN1 in osteosarcoma cells to investigate how they regulated migration, invasion, and epithelial-mesenchymal transition (EMT) of osteosarcoma cells in vitro. The nude mice were injected with osteosarcoma cell line with depleted PGM5-AS1 to detect the role of PGM5-AS1 in tumorigenesis in vivo.Results PGM5-AS1 possessing elevated level in osteosarcoma was identified as the differentially expressed lncRNA in osteosarcoma. Osteosarcoma tissues exhibited low miR-140-5p expression and high FBN1 expression. Results confirmed that PGM5-AS competitively bound to miR-140-5p to upregulate FBN1. Also, hindering PGM5-AS1 and FBN1 or enforcing miR-140-5p dampened migration, invasion, and EMT of osteosarcoma cells in vitro. Furthermore, silencing PGM5-AS1 markedly inhibited tumorigenesis in vivo.Conclusion All in all, PGM5-AS1 depletion causes FBN1 reduction to retard osteosarcoma processes by negatively modulating miR-140-5p, highlighting PGM5-AS1 silencing as a biomarker for osteosarcoma management.