Detection of lower levels of SNAP25 using multiple microarray systems and its functional significance in medulloblastoma

Int J Mol Med. 2017 May;39(5):1195-1205. doi: 10.3892/ijmm.2017.2925. Epub 2017 Mar 20.

Abstract

Medulloblastoma (MB) is the most common pediatric malignant brain tumor and patients with high-risk or recurrent MB respond poorly to current therapies, and have a higher related mortality. For this reason, potential molecules related to MB need be identified in order to develop targets for the development of novel therapeutics. In the present study, we compared MB microarray data obtained using different microarray systems and significant targets were selected by gene annotation and enrichment analysis. Genes for soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) annotated with the function 'vesicle' were identified and one of these proteins, synaptosomal-associated protein 25 (SNAP25), was found to have significantly lower expression levels in MB. In addition, SNAP25 was detected in a very low number of MB cells as shown by western blot analysis and immunohistochemical analyses of archived and formalin-fixed/paraffin-embedded human MB specimens. We found that SNAP25 altered the morphology and the chemotherapeutic effects of arabinofuranosyl cytidine (Ara-C) on SNAP25-expressing MB cells. On the whole, our data indicate that the expression of SNAP25 is crucial for dendrite formation and is associated with the effects of targeted chemotherapy. The detection of SNAP25 expression in MB cells may thus be essential for the chemotherapeutic application of Ara-C.

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Antimetabolites, Antineoplastic / pharmacology
  • Cell Line, Tumor
  • Cerebellar Neoplasms / diagnosis
  • Cerebellar Neoplasms / genetics*
  • Cerebellar Neoplasms / metabolism
  • Child
  • Cytarabine / pharmacology
  • Dendrites / drug effects
  • Dendrites / metabolism
  • Drug Resistance, Neoplasm / genetics
  • Female
  • Gene Expression Profiling*
  • Gene Expression Regulation, Neoplastic* / drug effects
  • Humans
  • Immunohistochemistry
  • Male
  • Medulloblastoma / diagnosis
  • Medulloblastoma / genetics*
  • Medulloblastoma / metabolism
  • Middle Aged
  • Prognosis
  • SNARE Proteins
  • Synaptosomal-Associated Protein 25 / genetics*
  • Synaptosomal-Associated Protein 25 / metabolism
  • Tissue Array Analysis
  • Transcriptome*
  • Young Adult

Substances

  • Antimetabolites, Antineoplastic
  • SNARE Proteins
  • Synaptosomal-Associated Protein 25
  • Cytarabine