JARID1B expression plays a critical role in chemoresistance and stem cell-like phenotype of neuroblastoma cells

Yung Ting Kuo, Yen-Lin Liu, Bamodu Oluwaseun Adebayo, Ping Hsiao Shih, Wei Hwa Lee, Liang Shun Wang, Yung Feng Liao, Wen Ming Hsu, Chi-Tai Yeh, Chien Min Lin

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article numbere0125343
JournalPLoS One
Volume10
Issue number5
DOIs
Publication statusPublished - May 7 2015

Fingerprint

Stem cells
Neuroblastoma
Amplification
stem cells
Tumors
Stem Cells
Histone Demethylases
Phenotype
phenotype
neoplasms
Cisplatin
Neoplasms
Cells
Modulation
cells
childhood
Pharmaceutical Preparations
therapeutics
neural crest
cisplatin

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

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.

In: PLoS One, Vol. 10, No. 5, e0125343, 07.05.2015.

Research output: Contribution to journalArticle

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