title: PHOX2B Is Associated with Neuroblastoma Cell Differentiation.
abstract: Neuroblastoma is a common pediatric malignancy that accounts for ∼15% of tumor-related deaths in children. The tumor is generally believed to originate from neural crest cells during early sympathetic neurogenesis. As the degree of neuroblastoma differentiation has been correlated with clinical outcome, clarifying the molecular mechanisms that drive neuroblastoma progression and differentiation is important for increasing the survival of these patients. In a previous study, the authors identified paired-like homeobox 2b (PHOX2B) as a key mediator of neuroblastoma pathogenesis in a TH-MYCN mouse model. In the present study, they aimed to define whether PHOX2B is also associated with proliferation and differentiation of human neuroblastoma cells. PHOX2B expression in neuroblastoma cells was evaluated by immunoblot analyses, and the effects of PHOX2B on the proliferation of neuroblastoma cells in vitro were determined using clonogenic and sphere formation assays. Xenograft experiments in NOD/SCID mice were used to examine the in vivo response to PHOX2B knockdown. Their data demonstrated that PHOX2B acts as a prognostic marker in neuroblastoma and that retinoic acid-induced neuronal differentiation downregulates PHOX2B expression, thereby suppressing the self-renewal capacity of neuroblastoma cells and inhibiting tumorigenicity. These findings confirmed that PHOX2B is a key regulator of neuroblastoma differentiation and stemness maintenance and indicated that PHOX2B might serve as a potential therapeutic target in neuroblastoma patients.
authors.affiliation: 1 Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University , Chongqing, P.R. China .
authors.forename: Liqun
authors.initials: L
authors.lastname: Yang
authors.affiliation: 1 Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University , Chongqing, P.R. China .
authors.forename: Xiao-Xue
authors.initials: XX
authors.lastname: Ke
authors.affiliation: 1 Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University , Chongqing, P.R. China .
authors.forename: Fan
authors.initials: F
authors.lastname: Xuan
authors.affiliation: 1 Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University , Chongqing, P.R. China .
authors.forename: Juan
authors.initials: J
authors.lastname: Tan
authors.affiliation: 1 Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University , Chongqing, P.R. China .
authors.forename: Jianbing
authors.initials: J
authors.lastname: Hou
authors.affiliation: 1 Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University , Chongqing, P.R. China .
authors.forename: Mei
authors.initials: M
authors.lastname: Wang
authors.affiliation: 1 Cell Biology Laboratory, State Key Laboratory of Silkworm Genome Biology, Southwest University , Chongqing, P.R. China .
authors.forename: Hongjuan
authors.initials: H
authors.lastname: Cui
authors.affiliation: 2 Department of Neurosurgery, Research Institute of Surgery, Daping Hospital, Third Military Medical University , Chongqing, P.R. China .
authors.forename: Yundong
authors.initials: Y
authors.lastname: Zhang
mesh_terms: D000818:Animals; D017209:Apoptosis; D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D015153:Blotting, Western; D002454:Cell Differentiation; D049109:Cell Proliferation; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D009367:Neoplasm Staging; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
chemical_list: D014408:Biomarkers, Tumor; D018398:Homeodomain Proteins; C109220:NBPhox protein; D012333:RNA, Messenger; D014157:Transcription Factors
keywords: PHOX2B; cell differentiation; neuroblastoma; stemness maintenance