Poster Presentation 46th Lorne Genome Conference 2025

Investigating the role of long non-coding RNAs in neuroblastoma development (#116)

Regina Belen P Callanta 1 2 , Xiaochun Li 2 , Andrew G Bert 2 , Yeesim Khew-Goodall 2 3 , Gregory J Goodall 2 3 , Lachlan 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 a childhood cancer that is hypothesised to occur when neural crest stem cells fail to differentiate during development of the sympathetic nervous system. To better understand regulation of this process, long non-coding RNAs (lncRNAs), RNAs that are >200 nucleotides in length with limited or no protein coding ability, were identified that change in expression by bulk and scRNA sequencing over a neuronal differentiation time course. From dozens that were identified, PHOX2B-AS1 is of particular interest because it is differentially expressed during neurogenesis, its role is uncharacterised, and its expression is inversely correlated with that of PHOX2B, an established master regulator in sympathetic neuronal differentiation. Knockdown of PHOX2B-AS1 using antisense oligonucleotides (ASOs) was performed and the expression of cell differentiation markers measured using qPCR. Preliminary findings indicate that knockdown of PHOX2B-AS1 inhibits proliferation and promotes differentiation, favouring the neuroblast lineage at the expense of chromaffin cell development. Further studies are needed to determine the regulatory role of PHOX2B-AS1 and its mechanism of action.