Member Domain 3 (LRIG3) Activates Hypoxia-Inducible Factor-1 α/Vascular Endothelial Growth Factor (HIF-1α/VEGF) Pathway to Inhibit the Growth of Bone Marrow Mesenchymal Stem Cells in Glioma

Abstract

Member domain 3 (LRIG3) of the LRIG gene family is down-regulated in several cancers. However, its role in bone marrow mesenchymal stem cells (BMSCs) in gliomas and the related mechanisms is unknown. The qRT-PCR assessed LRIG3 mRNA level. Rat BMSCs were randomly assigned into glioma group (BMSCs cultured in glioma microenvironment); LRIG3 overexpression group; and si-LRIG3 inhibitor group followed by analysis of LRIG3 expression, cell proliferation, PCNA and Ki-67 apoptosis, TNF-α; and HIF-1α/VEGF mRNA level. LRIG3 mRNA expression was decreased in gliomas patients (P < 0.05). BMSCs cultured in glioma microenvironment showed decreased LRIG3, increased cell proliferation, decreased PCNA, Ki-67 and TNF-α secretion as well as elevated HIF-1α and VEGF level (P < 0.05). Transfection of LRIG3 siRNA further promoted the above changes. Conversely, LRIG3 plasmid transfection significantly promoted its expression in glioma BMSCs (P < 0.05), inhibited cell proliferation, promoted PCNA, Ki-67, and TNF-α secretion, and increased HIF-1α and VEGF level (P < 0.05). LRIG3 in rat BMSCs cultured in the glioma microenvironment is decreased. Down-regulation of LRIG3 inhibits TNF-α secretion by activating HIF-1α/VEGF pathway regulating BMSCs proliferation and apoptosis.