title: JARID1B Expression Plays a Critical Role in Chemoresistance and Stem Cell-Like Phenotype of Neuroblastoma Cells.
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.
authors.affiliation: Department of Pediatrics, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Yung-Ting
authors.initials: YT
authors.lastname: Kuo
authors.affiliation: Degree Program of Translational Medicine, Academia Sinica-National Taiwan University, Taipei, Taiwan; Department of Pediatrics, Taipei Medical University Hospital, Taipei, Taiwan.
authors.forename: Yen-Lin
authors.initials: YL
authors.lastname: Liu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan.
authors.forename: Bamodu Oluwaseun
authors.initials: BO
authors.lastname: Adebayo
authors.affiliation: Department of Pediatrics, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Ping-Hsiao
authors.initials: PH
authors.lastname: Shih
authors.affiliation: Department of Pathology, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Wei-Hwa
authors.initials: WH
authors.lastname: Lee
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Division of Thoracic Surgery, Department of Surgery, Taipei Medical University- Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Liang-Shun
authors.initials: LS
authors.lastname: Wang
authors.affiliation: Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
authors.forename: Yung-Feng
authors.initials: YF
authors.lastname: Liao
authors.affiliation: Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Wen-Ming
authors.initials: WM
authors.lastname: Hsu
authors.affiliation: Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; Department of Medical Research and Education, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Chi-Tai
authors.initials: CT
authors.lastname: Yeh
authors.affiliation: Department of Neurosurgery, Taipei Medical University-Shuang Ho Hospital, Taipei, Taiwan.
authors.forename: Chien-Min
authors.initials: CM
authors.lastname: Lin
mesh_terms: D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D020868:Gene Silencing; D006801:Humans; D056484:Jumonji Domain-Containing Histone Demethylases / Q000235:genetics*; D014411:Neoplastic Stem Cells / Q000473:pathology*; D009447:Neuroblastoma / Q000188:drug therapy* / Q000473:pathology; D009687:Nuclear Proteins / Q000235:genetics*; D011379:Prognosis; D012097:Repressor Proteins / Q000235:genetics*
chemical_list: D009687:Nuclear Proteins; D012097:Repressor Proteins; D056484:Jumonji Domain-Containing Histone Demethylases; C119611:KDM5B protein, human