LAIR-1 overexpression inhibits osteosarcoma epithelial-mesenchymal transition via GLUT1-related energy metabolism
Abstract Background: Leukocyte-associated immunoglobulin-like receptor-1 (LAIR-1) is a collagen receptor belonging to the immunoglobulin superfamily. Although prior studies have evaluated the biological role of LAIR in solid tumors, the precise mechanisms underlying LAIR-1 functions as a regulator of tumor biological functions remains unclear. Methods: LAIR-1 expression was evaluated using an osteosarcoma (OS) tissue microarray by immunohistochemical analysis. Wound healing and Transwell assays were performed to evaluate tumor cell migration. Quantitative PCR and western blotting were conducted to detect the expression of epithelial-mesenchymal transition (EMT)-related molecules. RNA-sequencing (RNA-seq) was conducted to evaluate the mRNA expression profiles after overexpressing LAIR-1 in OS cells. Glucose uptake and glucose transporter (Glut) 1 expression in OS cells in vitro were evaluated by flow cytometry and western blotting. Results: LAIR-1 expression significantly differed between the T1 and T2 stages of OS tumors, and LAIR-1 overexpression inhibited OS cell migration. LAIR-1 expression was inversely correlated with the expression of EMT-associated transcription factors via the Forkhead box O1/Twist1 signal transduction pathway. Furthermore, RNA-seq and quantitative PCR demonstrated that EMT energy metabolism-related molecules were significantly reduced after LAIR-1 overexpression. Conclusions: Notably, overexpression of LAIR-1 in OS cells decreased Glut1 expression. These findings provide insight into the molecular mechanism underlying OS progression.