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Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling

Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein with frizzled-like cysteine-rich domain that binds with Wnt ligands or frizzled receptors to regulate Wnt signaling. SFRP2 is frequently hypermethylated in glioma patients, and analysis of TCGA data indicates that SFRP2 is one of the most...

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Autores principales: Wu, Quansheng, Yin, Xiaofeng, Zhao, Wenbo, Xu, Wenli, Chen, Laizhao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635357/
https://www.ncbi.nlm.nih.gov/pubmed/34852024
http://dx.doi.org/10.1371/journal.pone.0260864
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author Wu, Quansheng
Yin, Xiaofeng
Zhao, Wenbo
Xu, Wenli
Chen, Laizhao
author_facet Wu, Quansheng
Yin, Xiaofeng
Zhao, Wenbo
Xu, Wenli
Chen, Laizhao
author_sort Wu, Quansheng
collection PubMed
description Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein with frizzled-like cysteine-rich domain that binds with Wnt ligands or frizzled receptors to regulate Wnt signaling. SFRP2 is frequently hypermethylated in glioma patients, and analysis of TCGA data indicates that SFRP2 is one of the most downregulated genes in radiotherapy treated glioma patients. In the present study, we aimed to explore the potential function of SFRP2 in tumorigenesis and radioresistance of glioma. The RNA sequencing data of TCGA glioma samples were downloaded and analyzed. SFRP2 expression in 166 glioma patients was evaluated by qRT-PCR. The potential functions of SFRP2 in glioma were evaluated by loss-of-function assays and gain-of-function assays in glioma cell lines. We found that SFRP2 was downregulated in radiotherapy-treated glioma patients, and low SFRP2 expression was correlated with advanced tumor stage and poor prognosis. CRISP/Cas9-meidated SFRP2 knockdown promoted soft agar colony formation, cancer stemness and radioresistance of glioma cells, while enforced SFRP2 expression exhibited opposite effects. Moreover, Wnt/β-catenin signaling was activated in radiotherapy treated glioma patients. SFRP2 knockdown activated Wnt/β-catenin signaling in glioma cell lines, while overexpression of SFRP2 inhibited Wnt/β-catenin activation. Besides, pharmacological inhibition of Wnt/β-catenin signaling by XAV-939 abrogated the effects of SFRP2 knockdown on cancer stemness and radioresistance of glioma cells. Our data for the first time demonstrated a role of SFRP2 in radioresistance of glioma cells, and suggested that inhibition of Wnt/β-catenin signaling might be a potential strategy for increasing radiosensitivity of glioma patients.
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spelling pubmed-86353572021-12-02 Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling Wu, Quansheng Yin, Xiaofeng Zhao, Wenbo Xu, Wenli Chen, Laizhao PLoS One Research Article Secreted frizzled-related protein 2 (SFRP2) is a glycoprotein with frizzled-like cysteine-rich domain that binds with Wnt ligands or frizzled receptors to regulate Wnt signaling. SFRP2 is frequently hypermethylated in glioma patients, and analysis of TCGA data indicates that SFRP2 is one of the most downregulated genes in radiotherapy treated glioma patients. In the present study, we aimed to explore the potential function of SFRP2 in tumorigenesis and radioresistance of glioma. The RNA sequencing data of TCGA glioma samples were downloaded and analyzed. SFRP2 expression in 166 glioma patients was evaluated by qRT-PCR. The potential functions of SFRP2 in glioma were evaluated by loss-of-function assays and gain-of-function assays in glioma cell lines. We found that SFRP2 was downregulated in radiotherapy-treated glioma patients, and low SFRP2 expression was correlated with advanced tumor stage and poor prognosis. CRISP/Cas9-meidated SFRP2 knockdown promoted soft agar colony formation, cancer stemness and radioresistance of glioma cells, while enforced SFRP2 expression exhibited opposite effects. Moreover, Wnt/β-catenin signaling was activated in radiotherapy treated glioma patients. SFRP2 knockdown activated Wnt/β-catenin signaling in glioma cell lines, while overexpression of SFRP2 inhibited Wnt/β-catenin activation. Besides, pharmacological inhibition of Wnt/β-catenin signaling by XAV-939 abrogated the effects of SFRP2 knockdown on cancer stemness and radioresistance of glioma cells. Our data for the first time demonstrated a role of SFRP2 in radioresistance of glioma cells, and suggested that inhibition of Wnt/β-catenin signaling might be a potential strategy for increasing radiosensitivity of glioma patients. Public Library of Science 2021-12-01 /pmc/articles/PMC8635357/ /pubmed/34852024 http://dx.doi.org/10.1371/journal.pone.0260864 Text en © 2021 Wu et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Wu, Quansheng
Yin, Xiaofeng
Zhao, Wenbo
Xu, Wenli
Chen, Laizhao
Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling
title Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling
title_full Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling
title_fullStr Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling
title_full_unstemmed Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling
title_short Downregulation of SFRP2 facilitates cancer stemness and radioresistance of glioma cells via activating Wnt/β-catenin signaling
title_sort downregulation of sfrp2 facilitates cancer stemness and radioresistance of glioma cells via activating wnt/β-catenin signaling
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8635357/
https://www.ncbi.nlm.nih.gov/pubmed/34852024
http://dx.doi.org/10.1371/journal.pone.0260864
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