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学科主题: 临床医学
题名:
Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo
作者: Wang, Dongliang; Zhou, Jingru; Fan, Cungang; Jiao, Feng; Liu, Bo; Sun, Peng; Miao, Junjie; Zhang, Qingjun
关键词: glioma ; LGR5 ; proliferation ; orthotopic xenograft ; siRNA
刊名: ONCOLOGY REPORTS
发表日期: 2014
DOI: 10.3892/or.2013.2826
卷: 31, 期:1, 页:41-49
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Oncology
研究领域[WOS]: Oncology
关键词[WOS]: COUPLED RECEPTOR GPR49 ; STEM-CELLS ; WNT/BETA-CATENIN ; POOR-PROGNOSIS ; WNT RECEPTORS ; SELF-RENEWAL ; R-SPONDINS ; GLIOBLASTOMA ; SURVIVAL ; CANCER
英文摘要:

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.

语种: 英语
所属项目编号: RDB2011-14
项目资助者: Peking University People&prime ; s Hospital Research and Development Funds
WOS记录号: WOS:000330788100006
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61142
Appears in Collections:北京大学第二临床医学院_神经外科_期刊论文

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作者单位: Peking Univ, Peoples Hosp, Dept Neurosurg, Beijing 100044, Peoples R China

Recommended Citation:
Wang, Dongliang,Zhou, Jingru,Fan, Cungang,et al. Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo[J]. ONCOLOGY REPORTS,2014,31(1):41-49.
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