JARID1B expression plays a critical role in chemoresistance and stem cell-like phenotype of neuroblastoma cells
Journal
PLoS ONE
Journal Volume
10
Journal Issue
5
Date Issued
2015
Author(s)
Kuo Y.-T.
Liu Y.-L.
Adebayo B.O.
Shih P.-H.
Lee W.-H.
Wang L.-S.
Liao Y.-F.
Yeh C.-T.
Lin C.-M.
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. ? 2015 Kuo et al.
SDGs
Other Subjects
cisplatin; doxorubicin; etoposide; histone demethylase; Jagged protein; membrane protein; Notch receptor; oncoprotein; protein JARID1B; unclassified drug; histone demethylase; KDM5B protein, human; nuclear protein; repressor protein; Article; cancer stem cell; controlled study; down regulation; drug resistance; drug sensitivity; gene; gene amplification; human; human cell; MYCN gene; neuroblastoma; neuroblastoma cell line; phenotype; protein expression; protein function; signal transduction; tumor invasion; tumor spheroid; cancer stem cell; gene silencing; genetics; neuroblastoma; pathology; prognosis; tumor cell line; Cell Line, Tumor; Drug Resistance, Neoplasm; Gene Silencing; Humans; Jumonji Domain-Containing Histone Demethylases; Neoplastic Stem Cells; Neuroblastoma; Nuclear Proteins; Prognosis; Repressor Proteins
Publisher
Public Library of Science
Type
journal article