Poster Presentation 47th Lorne Genome Conference 2026

Investigating the regulatory roles of microRNA clusters in neuroblastoma development (133074)

Regina Belen P Callanta 1 , Xiaochun Li 2 , Andrew G Bert 2 , Aayushi Notra 2 , Katherine A Pillman 2 3 , Quenten Schwarz 2 3 , Yeesim Khew-Goodall 2 3 , Gregory J Goodall 2 3 , Lachlan A Jolly 1 , Cameron P Bracken 1 2 3
  1. School of Biomedicine, University of Adelaide, Adelaide, SA, Australia
  2. Centre for Cancer Biology, University of South Australia, Adelaide, South Australia, Australia
  3. School of Medicine, University of Adelaide, Adelaide, SA, Australia

Neuroblastoma (NB) is the most common extra-cranial solid tumour in children, accounting for ~15% of cancer-related deaths. It is a childhood cancer that is hypothesised to occur when migrating neural crest cells fail to differentiate during development of the sympathetic nervous system. To better understand underlying molecular causes of NB, we have employed human induced pluripotent stem cells (iPSCs) as a model system to recapitulate sympathetic neuronal differentiation and using bulk and scRNA sequencing, we have identified 13 microRNA (miR) clusters that are regulated during development. Of these, 8 miR clusters were successfully cloned into Doxycycline (Dox)-inducible vectors to maintain their expression over the iPSC neuronal differentiation time course. Overexpression of the miR-17-92 cluster results in the upregulation of MYCN, a common oncogenic driver of NB, and NTRK1, a marker of sympathetic ganglion. The maintenance of miR-15a-16 expression resulted in the upregulation of PHOX2B and ALK, known drivers of familial NB. Maintenance of miR-182-183 promoted the expression of early differentiation markers; FOXD3 and SOX10. Work is ongoing to determine the regulatory roles of these 3 miR clusters (miR-17-92, miR-182-183, and miR-15a-16) in both normal development and in NB.

  1. American Childhood Cancer Registry, 2006-2015
  2. Meredith S. Irwin et al. 2021. Revised Neuroblastoma Risk Classification System: A Report From the Children's Oncology Group.