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Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB

Although cyclophilin A (CypA) has been reported to be over-expressed in cancer cells and solid tumors, its expression and role in glioblastomas have not been studied. Herein, we show that expression of CypA in human glioblastoma cell lines and tissues is significantly higher than in normal human ast...

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Autores principales: Sun, Shan, Wang, Qiuwei, Giang, An, Cheng, Cong, Soo, Chia, Wang, Cun-Yu, Liau, Linda M., Chiu, Robert
Formato: Texto
Lenguaje:English
Publicado: Springer US 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995866/
https://www.ncbi.nlm.nih.gov/pubmed/20454998
http://dx.doi.org/10.1007/s11060-010-0220-y
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author Sun, Shan
Wang, Qiuwei
Giang, An
Cheng, Cong
Soo, Chia
Wang, Cun-Yu
Liau, Linda M.
Chiu, Robert
author_facet Sun, Shan
Wang, Qiuwei
Giang, An
Cheng, Cong
Soo, Chia
Wang, Cun-Yu
Liau, Linda M.
Chiu, Robert
author_sort Sun, Shan
collection PubMed
description Although cyclophilin A (CypA) has been reported to be over-expressed in cancer cells and solid tumors, its expression and role in glioblastomas have not been studied. Herein, we show that expression of CypA in human glioblastoma cell lines and tissues is significantly higher than in normal human astrocytes and normal counterparts of brain tissue. To determine the role of over-expressed CypA in glioblastoma, stable RNA interference (RNAi)-mediated knockdown of CypA (CypA KD) was performed in gliobastoma cell line U87vIII (U87MG · ΔEGFR). CypA KD stable single clones decrease proliferation, infiltration, migration, and anchorage-independent growth in vitro and with slower growth in vivo as xenografts in immunodeficient nude mice. We have also observed that knockdown of CypA inhibits expression of interleukin-8 (IL-8), a tumorigenic and proangiogenic cytokine. Conversely, enforced expression of CypA in the CypA KD cell line, Ud-12, markedly enhanced IL-8 transcripts and restored Ud-12 proliferation, suggesting that CypA-mediated IL-8 production provides a growth advantage to glioblastoma cells. CypA knockdown-mediated inhibition of IL-8 is due to reduced activity of NF-κB, which is one of the major transcription factors regulating IL-8 expression. These results not only establish the relevance of CypA to glioblastoma growth in vitro and in vivo, but also suggest that small interfering RNA-based CypA knockdown could be an effective therapeutic approach against glioblastomas.
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spelling pubmed-29958662011-01-04 Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB Sun, Shan Wang, Qiuwei Giang, An Cheng, Cong Soo, Chia Wang, Cun-Yu Liau, Linda M. Chiu, Robert J Neurooncol Laboratory Investigation - Human/Animal Tissue Although cyclophilin A (CypA) has been reported to be over-expressed in cancer cells and solid tumors, its expression and role in glioblastomas have not been studied. Herein, we show that expression of CypA in human glioblastoma cell lines and tissues is significantly higher than in normal human astrocytes and normal counterparts of brain tissue. To determine the role of over-expressed CypA in glioblastoma, stable RNA interference (RNAi)-mediated knockdown of CypA (CypA KD) was performed in gliobastoma cell line U87vIII (U87MG · ΔEGFR). CypA KD stable single clones decrease proliferation, infiltration, migration, and anchorage-independent growth in vitro and with slower growth in vivo as xenografts in immunodeficient nude mice. We have also observed that knockdown of CypA inhibits expression of interleukin-8 (IL-8), a tumorigenic and proangiogenic cytokine. Conversely, enforced expression of CypA in the CypA KD cell line, Ud-12, markedly enhanced IL-8 transcripts and restored Ud-12 proliferation, suggesting that CypA-mediated IL-8 production provides a growth advantage to glioblastoma cells. CypA knockdown-mediated inhibition of IL-8 is due to reduced activity of NF-κB, which is one of the major transcription factors regulating IL-8 expression. These results not only establish the relevance of CypA to glioblastoma growth in vitro and in vivo, but also suggest that small interfering RNA-based CypA knockdown could be an effective therapeutic approach against glioblastomas. Springer US 2010-05-09 2011 /pmc/articles/PMC2995866/ /pubmed/20454998 http://dx.doi.org/10.1007/s11060-010-0220-y Text en © The Author(s) 2010 https://creativecommons.org/licenses/by-nc/4.0/ This article is distributed under the terms of the Creative Commons Attribution Noncommercial License which permits any noncommercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.
spellingShingle Laboratory Investigation - Human/Animal Tissue
Sun, Shan
Wang, Qiuwei
Giang, An
Cheng, Cong
Soo, Chia
Wang, Cun-Yu
Liau, Linda M.
Chiu, Robert
Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB
title Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB
title_full Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB
title_fullStr Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB
title_full_unstemmed Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB
title_short Knockdown of CypA inhibits interleukin-8 (IL-8) and IL-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated NF-κB
title_sort knockdown of cypa inhibits interleukin-8 (il-8) and il-8-mediated proliferation and tumor growth of glioblastoma cells through down-regulated nf-κb
topic Laboratory Investigation - Human/Animal Tissue
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2995866/
https://www.ncbi.nlm.nih.gov/pubmed/20454998
http://dx.doi.org/10.1007/s11060-010-0220-y
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