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

Abstract

Osteosarcoma is an uncommon tumor occurring in bone, accompanied by elevated incidence and reduced rate of healing. Epithelial-to-mesenchymal transition (EMT) serves as a conceptual paradigm to explain the invasion and metastasis of osteosarcoma and other cancers. Hence, developing effective therapeutic strategy to treat the EMT of osteosarcoma is essential. Here, we identified the molecular mechanism of long noncoding RNA (lncRNA) PGM5-AS1 in EMT and progression of osteosarcoma. Microarray-based analysis was employed to screen the osteosarcoma-related differentially expressed lncRNAs. The levels of PGM5-AS1 as well as microRNA-140-5p (miR-140-5p) and fibrillin-1 (FBN1) in osteosarcoma tissues and cells were determined. Dual-luciferase reporter gene assay, RNA pull-down assay, and RNA immunoprecipitation assay were conducted to validate the relationship among PGM5-AS1, miR-140-5p, and FBN1. Expression of PGM5-AS1, miR-140-5p, and FBN1 was altered by overexpression, shRNA, mimic, or inhibitors in order to investigate how they regulated migration, invasion, and EMT of osteosarcoma cells in vitro. Loss- and gain-of-function approaches were employed in nude mice to detect their roles in tumorigenesis in vivo. Osteosarcoma tissues and cells exhibited low expression of miR-140-5p, but high expression of PGM5-AS1 and FBN1. PGM5-AS1 competitively bound to miR-140-5p to upregulate FBN1. Furthermore, hindering PGM5-AS1 and FBN1 or overexpressing miR-140-5p dampened migration, invasion, and EMT of osteosarcoma cells in vitro. Furthermore, silencing PGM5-AS1 or FBN1, or overexpressing miR-140-5p markedly inhibited tumorigenesis in nude mice in vivo. Taken together, PGM5-AS1 depletion causes FBN1 reduction to retard osteosarcoma processes by negatively modulating miR-140-5p.

• Authors: Wei Liu, Pengcheng Liu, Hang Gao, Xu Wang, Ming Yan
• Journal: Molecular oncology (Mol Oncol) Vol. 14 Issue 10 Pg. 2660-2677 (10 2020) ISSN: 1878-0261 [Electronic] United States
• PMID: 32412676 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Retracted Publication)
• Copyright: © 2020 The Authors. published by FEBS press John Wiley & Sons Ltd.

Chemical References

• FBN1 protein, human
• Fibrillin-1
• MicroRNAs
• Mirn140 microRNA, human
• RNA, Long Noncoding

Topics

• Animals
• Base Sequence
• Carcinogenesis (genetics, pathology)
• Cell Line, Tumor
• Cell Movement (genetics)
• Disease Progression
• Epithelial-Mesenchymal Transition (genetics)
• Female
• Fibrillin-1 (antagonists & inhibitors, genetics, metabolism)
• Gene Expression Regulation, Neoplastic
• Gene Silencing
• Humans
• Male
• Mice, Nude
• MicroRNAs (genetics, metabolism)
• Neoplasm Invasiveness
• Neoplasm Metastasis
• Osteosarcoma (genetics, pathology)
• RNA, Long Noncoding (genetics, metabolism)
• Up-Regulation (genetics)
• Young Adult