Kuo Y.-T.Liu Y.-L.Adebayo B.O.Shih P.-H.Lee W.-H.Wang L.-S.Liao Y.-F.WEN-MING HSUYeh C.-T.Lin C.-M.2020-03-052020-03-0520151932-6203https://www.scopus.com/inward/record.uri?eid=2-s2.0-84929096035&doi=10.1371%2fjournal.pone.0125343&partnerID=40&md5=5fd270b025af80e04a8c364aa303c5d4https://scholars.lib.ntu.edu.tw/handle/123456789/469983Neuroblastoma (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]SDG3cisplatin; 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 Proteinsjournal article10.1371/journal.pone.0125343259512382-s2.0-84929096035