Cargando…

Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo

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 investiga...

Descripción completa

Detalles Bibliográficos
Autores principales: WANG, DONGLIANG, ZHOU, JINGRU, FAN, CUNGANG, JIAO, FENG, LIU, BO, SUN, PENG, MIAO, JUNJIE, ZHANG, QINGJUN
Formato: Online Artículo Texto
Lenguaje:English
Publicado: D.A. Spandidos 2014
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868492/
https://www.ncbi.nlm.nih.gov/pubmed/24172981
http://dx.doi.org/10.3892/or.2013.2826
_version_ 1782296455512326144
author WANG, DONGLIANG
ZHOU, JINGRU
FAN, CUNGANG
JIAO, FENG
LIU, BO
SUN, PENG
MIAO, JUNJIE
ZHANG, QINGJUN
author_facet WANG, DONGLIANG
ZHOU, JINGRU
FAN, CUNGANG
JIAO, FENG
LIU, BO
SUN, PENG
MIAO, JUNJIE
ZHANG, QINGJUN
author_sort WANG, DONGLIANG
collection PubMed
description 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.
format Online
Article
Text
id pubmed-3868492
institution National Center for Biotechnology Information
language English
publishDate 2014
publisher D.A. Spandidos
record_format MEDLINE/PubMed
spelling pubmed-38684922013-12-20 Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo WANG, DONGLIANG ZHOU, JINGRU FAN, CUNGANG JIAO, FENG LIU, BO SUN, PENG MIAO, JUNJIE ZHANG, QINGJUN Oncol Rep Articles 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. D.A. Spandidos 2014-01 2013-10-31 /pmc/articles/PMC3868492/ /pubmed/24172981 http://dx.doi.org/10.3892/or.2013.2826 Text en Copyright © 2014, Spandidos Publications http://creativecommons.org/licenses/by/3.0 This is an open-access article licensed under a Creative Commons Attribution-NonCommercial 3.0 Unported License. The article may be redistributed, reproduced, and reused for non-commercial purposes, provided the original source is properly cited.
spellingShingle Articles
WANG, DONGLIANG
ZHOU, JINGRU
FAN, CUNGANG
JIAO, FENG
LIU, BO
SUN, PENG
MIAO, JUNJIE
ZHANG, QINGJUN
Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo
title Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo
title_full Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo
title_fullStr Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo
title_full_unstemmed Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo
title_short Knockdown of LGR5 suppresses the proliferation of glioma cells in vitro and in vivo
title_sort knockdown of lgr5 suppresses the proliferation of glioma cells in vitro and in vivo
topic Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3868492/
https://www.ncbi.nlm.nih.gov/pubmed/24172981
http://dx.doi.org/10.3892/or.2013.2826
work_keys_str_mv AT wangdongliang knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo
AT zhoujingru knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo
AT fancungang knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo
AT jiaofeng knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo
AT liubo knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo
AT sunpeng knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo
AT miaojunjie knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo
AT zhangqingjun knockdownoflgr5suppressestheproliferationofgliomacellsinvitroandinvivo