Leucine-rich repeat containing
G protein-coupled receptor 5 (LGR5), one of the target genes of the Wnt signaling pathway, has recently been identified as a marker for
brain cancer stem-like cells. However, the role of LGR5 in
glioma is poorly understood. The aim of the present study was to investigate the relationship between LGR5 expression and pathological grade in
glioma, and the impact of LGR5 on the proliferation of
glioma cells in vitro and in vivo. Firstly, LGR5 expression was immunohistochemically evaluated in 54 resected
gliomas of different pathologic grades, and its association with Ki-67 was evaluated. Subsequently, using western blotting and qRT-PCR, the expression of LGR5 was assessed in three
glioma cell lines U87, U118 and U251. Moreover, the effects of LGR5 knockdown by
siRNA on
glioma cell proliferation, cell cycle, clone formation and tumorsphere formation in vitro and gliomagenesis in vivo were assessed. The results revealed that i) LGR5 was positively expressed in all
glioma specimens and its expression increased with pathologic grade and Ki-67 expression; ii) LGR5 was highly expressed in three
glioma cell lines and its expression was reduced significantly by
siRNA; and iii) RNAi-mediated downregulation of endogenous LGR5 in U87 cells resulted in the suppression of cell proliferation, arrest of the cell cycle, and reduction in clone and tumorsphere formation in vitro. In addition, LGR5 depletion significantly inhibited
tumor orthotopic xenograft growth in nude mice. These findings indicate that LGR5 plays a major role in gliomagenesis by promoting neoplastic cell proliferation, suggesting LGR5 as a molecular marker for pathology and a novel therapeutic target for
malignant glioma.