LAIR-1 overexpression inhibits epithelial–mesenchymal transition in osteosarcoma 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 previous studies have evaluated the biological role of LAIR in solid tumors, the precise mechanisms underlying the functions of LAIR-1 as a regulator of tumor biological functions remain unclear.Methods: LAIR-1 expression was evaluated by immunohistochemical analysis using an osteosarcoma (OS) tissue microarray. Wound healing and transwell migration assays were performed to evaluate tumor cell migration. Quantitative real-time polymerase chain reaction (qPCR) 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 transporter (Glut)1 expression in OS cells was evaluated by western blotting.Results: LAIR-1 expression was significantly different between the T1 and T2 stages of OS tumors, and it inhibited OS cell migration. LAIR-1 expression was inversely correlated with the expression of Twist1, an EMT-associated transcription factor, via the Forkhead box O1 signal transduction pathway. Furthermore, RNA-seq and qPCR demonstrated that the expression of EMT energy metabolism-related molecules was significantly reduced after LAIR-1 overexpression.Conclusions: LAIR-1 overexpression decreased the expression of Glut1 and inhibited the expression of EMT-related molecules in OS cells. These findings provide new insights into the molecular mechanism underlying OS progression.

Regulatory Effects and Mechanism of Immune Inhibitory Receptor LAIR-1 in Non-small Cell Lung Cancer

“…To explore the biological effect of LAIR-1 in vitro, David et al reported that knockdown of LAIR-1 signi cantly inhibited leukemia cell growth and increased apoptosis (Guo et al, 2020). Zhang et al found that LAIR-1 inhibited osteosarcoma cell migration because the overexpression of LAIR-1 dramatically regulated the expression of EMT-related proteins in OS cells through phosphorylating Twist1, a downstream function of Foxo1 (Zhang et al, 2020). Fu et al (Cao et al, 2015) demonstrated that in the cervical cancer cells, overexpression of LAIR-1 inhibited cell proliferation and promoted cell apoptotic capacity.…”