Stathmin regulation of microRNA/mRNA expression in neuroblastoma cells — ASN Events
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  3. Stathmin regulation of microRNA/mRNA expression in neuroblastoma cells

Stathmin regulation of microRNA/mRNA expression in neuroblastoma cells (#140)

Sela Po'uha 1 2 , Miriam Brandl 1 2 , Maria Kavallaris 1 2
  1. Children’s Cancer Institute, Lowy Cancer Research Centre, University of New South Wales, Randwick, NSW, Australia
  2. ARC Centre of Convergent Bio-Nano Science and Technology, Australian Centre for Nanomedicine, University of New South Wales, Sydney, NSW, Australia

Advanced stage neuroblastoma is a highly aggressive childhood cancer. Widely-disseminated, metastatic disease at diagnosis is frequently observed and confers a poor prognosis. There is an urgent need to identify how metastasis occurs and ways to target metastatic disease. Stathmin is a microtubule-destabilising phosphoprotein that is overexpressed in many cancers including neuroblastoma. We recently showed that stathmin mediates neuroblastoma cell migration and invasion in vitro and metastasis in vivo (1). Several studies have identified a number of microRNAs (miRNAs) that play an important role in neuroblastoma cell proliferation, migration, invasion and metastasis. Therefore, we hypothesised that stathmin regulates the expression of miRNAs and that these are involved in stathmin-mediated neuroblastoma metastasis. To identify miRNAs that are differentially regulated by stathmin, we performed Affymetrix GeneChip miRNA 3.0 arrays in stathmin depleted and control neuroblastoma cells. In order to integrate miRNA changes with the expression of their target genes we also performed gene expression analysis using the Affymetrix Human 2.0 Gene ST Array. We identified 12 differentially expressed miRNAs in the stathmin depleted neuroblastoma cells compared to the control cells. Expression of three of these miRNAs was validated by qPCR in two independent neuroblastoma cell lines that have stable suppression of stathmin. Integration of miRNA and gene expression revealed target genes that were significantly altered in stathmin depleted cells. Downstream analysis will focus on genes with expression levels negatively correlated to that of their targeting miRNA. Interestingly, pathway analysis of the target genes identified a number of key signalling pathways involved in cell migration, metastasis and cell survival. Collectively, we have identified specific miRNAs and their predicted target genes that are modulated by stathmin, revealing signalling pathway(s) potentially involved in stathmin-mediated metastasis in neuroblastoma. These differentially expressed miRNAs and their target genes will be explored as potential therapeutic targets for treating metastatic neuroblastoma.

  1. Byrne FL, Yang L, Phillips PA, Hansford LM, Fletcher JI, Ormandy CJ, McCarroll JA, Kavallaris M. RNAi-mediated stathmin suppression reduces lung metastasis in an orthotopic neuroblastoma mouse model. Oncogene. 2014;33(7):882-90.