title: Dihydropyrimidinase-like protein 3 expression is negatively regulated by MYCN and associated with clinical outcome in neuroblastoma.
abstract: Dihydropyrimidinase-like proteins (DPYSLs) are a family of proteins developmentally regulated during maturation of the nervous system. Recently, members of the DPYSL family have been reported to be involved in cancer with low expression of DPYSL1 correlating with poor clinical outcomes in non-small cell lung cancer and functioning as a metastasis suppressor. Neuroblastoma (NB) is a tumor derived from precursor cells of the sympathetic nervous system and is the most common solid tumor in childhood. So far the biological functions of DPYSLs in NB remain elusive. Studying the potential roles of DPYSLs in NB may give us new insights into NB tumorigenesis. In the present study, using antibodies specific to different members of the DPYSL family, DPYSL1, DPYSL2 and DPYSL3, we investigated regulation of their expression and their subcellular distribution during retinoic acid (RA)-induced differentiation in NB cells. The correlation between DPYSLs and MYCN, a biomarker for poor prognosis of NB, was evaluated. We found that DPYSL3 levels increased during RA-induced cell differentiation. Downregulation of MYCN by small interfering RNA (siRNA) increased DPYSL3 levels, while upregulation of MYCN in non-MYCN NB cells decreased DPYSL3 levels. DPYSL1 and DPYSL2 expression didn't change during RA treatment or under different expression levels of MYCN. Moreover, a high level of DPYSL3 mRNA, but not that of DPYSL1 or DPYSL2 mRNA, was detected in tumors from advanced-stage NB that have a better survival. These data indicated that DPYSL3, not DPYSL1 or DPYSL2, is negatively regulated by MYCN and may be used as a potential biomarker for NB.
authors.affiliation: Department of Neurology, Shengjing Hospital of China Medical University, Shenyang, China; Cell & Molecular Biology Section, Pediatric Oncology Branch, National Cancer Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Tan
authors.forename: Reema
authors.initials: R
authors.lastname: Wahdan-Alaswad
authors.forename: Shuang
authors.initials: S
authors.lastname: Yan
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Thiele
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Li
mesh_terms: D014408:Biomarkers, Tumor / Q000096:biosynthesis; D002454:Cell Differentiation / Q000187:drug effects; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics; D009124:Muscle Proteins / Q000096:biosynthesis* / Q000235:genetics; D000071447:N-Myc Proto-Oncogene Protein; D009419:Nerve Tissue Proteins / Q000235:genetics; D009447:Neuroblastoma / Q000235:genetics / Q000378:metabolism*; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D011379:Prognosis; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D013564:Sympathetic Nervous System / Q000378:metabolism; D014212:Tretinoin; D015854:Up-Regulation; D000098855:Collapsin Response Mediator Protein 1
chemical_list: D014408:Biomarkers, Tumor; D036341:Intercellular Signaling Peptides and Proteins; D009124:Muscle Proteins; D000071447:N-Myc Proto-Oncogene Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D014212:Tretinoin; C102924:CRMP1 protein, human; D000098855:Collapsin Response Mediator Protein 1; C102926:DPYSL3 protein, human; C459801:MYCN protein, human; C095114:collapsin response mediator protein-2