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JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells

Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited t...

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Autores principales: Kuo, Yung-Ting, Liu, Yen-Lin, Adebayo, Bamodu Oluwaseun, Shih, Ping-Hsiao, Lee, Wei-Hwa, Wang, Liang-Shun, Liao, Yung-Feng, Hsu, Wen-Ming, Yeh, Chi-Tai, Lin, Chien-Min
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423965/
https://www.ncbi.nlm.nih.gov/pubmed/25951238
http://dx.doi.org/10.1371/journal.pone.0125343
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author Kuo, Yung-Ting
Liu, Yen-Lin
Adebayo, Bamodu Oluwaseun
Shih, Ping-Hsiao
Lee, Wei-Hwa
Wang, Liang-Shun
Liao, Yung-Feng
Hsu, Wen-Ming
Yeh, Chi-Tai
Lin, Chien-Min
author_facet Kuo, Yung-Ting
Liu, Yen-Lin
Adebayo, Bamodu Oluwaseun
Shih, Ping-Hsiao
Lee, Wei-Hwa
Wang, Liang-Shun
Liao, Yung-Feng
Hsu, Wen-Ming
Yeh, Chi-Tai
Lin, Chien-Min
author_sort Kuo, Yung-Ting
collection PubMed
description Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited treatment options and associated with poor prognosis. This necessitates the need for novel effective therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine demethylase, identified as an oncogene in many cancer types. Clinical data obtained from freely-accessible databases show a negative correlation between JARID1B expression and survival rates. Here, we demonstrated for the first time the role of JARID1B in the enhancement of stem cell-like activities and drug resistance in NB cells. We showed that JARID1B may be overexpressed in either MYCN amplification (SK-N-BE(2)) or MYCN-non-amplified (SK-N-SH and SK-N-FI) cell lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2) and SK-N-DZ. Moreover, SK-N-BE(2) spheroids were more resistant to chemotherapeutics as compared to parental cells. In addition, we demonstrated that JARID1B-silenced cells acquired a decreased propensity for tumor invasion and tumorsphere formation, but increased sensitivity to cisplatin treatment. Mechanistically, reduced JARID1B expression led to the downregulation of Notch/Jagged signaling. Collectively, we provided evidence that JARID1B via modulation of stemness-related signaling is a putative novel therapeutic target for treating malignant NB.
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spelling pubmed-44239652015-05-13 JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells Kuo, Yung-Ting Liu, Yen-Lin Adebayo, Bamodu Oluwaseun Shih, Ping-Hsiao Lee, Wei-Hwa Wang, Liang-Shun Liao, Yung-Feng Hsu, Wen-Ming Yeh, Chi-Tai Lin, Chien-Min PLoS One Research Article Neuroblastoma (NB) is a common neural crest-derived extracranial solid cancer in children. Among all childhood cancers, NB causes devastating loss of young lives as it accounts for 15% of childhood cancer mortality. Neuroblastoma, especially high-risk stage 4 NB with MYCN amplification has limited treatment options and associated with poor prognosis. This necessitates the need for novel effective therapeutic strategy. JARID1B, also known as KDM5B, is a histone lysine demethylase, identified as an oncogene in many cancer types. Clinical data obtained from freely-accessible databases show a negative correlation between JARID1B expression and survival rates. Here, we demonstrated for the first time the role of JARID1B in the enhancement of stem cell-like activities and drug resistance in NB cells. We showed that JARID1B may be overexpressed in either MYCN amplification (SK-N-BE(2)) or MYCN-non-amplified (SK-N-SH and SK-N-FI) cell lines. JARID1B expression was found enriched in tumor spheres of SK-N-BE(2) and SK-N-DZ. Moreover, SK-N-BE(2) spheroids were more resistant to chemotherapeutics as compared to parental cells. In addition, we demonstrated that JARID1B-silenced cells acquired a decreased propensity for tumor invasion and tumorsphere formation, but increased sensitivity to cisplatin treatment. Mechanistically, reduced JARID1B expression led to the downregulation of Notch/Jagged signaling. Collectively, we provided evidence that JARID1B via modulation of stemness-related signaling is a putative novel therapeutic target for treating malignant NB. Public Library of Science 2015-05-07 /pmc/articles/PMC4423965/ /pubmed/25951238 http://dx.doi.org/10.1371/journal.pone.0125343 Text en © 2015 Kuo et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Kuo, Yung-Ting
Liu, Yen-Lin
Adebayo, Bamodu Oluwaseun
Shih, Ping-Hsiao
Lee, Wei-Hwa
Wang, Liang-Shun
Liao, Yung-Feng
Hsu, Wen-Ming
Yeh, Chi-Tai
Lin, Chien-Min
JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells
title JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells
title_full JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells
title_fullStr JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells
title_full_unstemmed JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells
title_short JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells
title_sort jarid1b expression plays a critical role in chemoresistance and stem cell-like phenotype of neuroblastoma cells
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4423965/
https://www.ncbi.nlm.nih.gov/pubmed/25951238
http://dx.doi.org/10.1371/journal.pone.0125343
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