Pediatric Infectious Diseases: Open Access

Validation of novel growth-promoting and growth-suppressing genes in neuroblastoma cells

Neuroblastoma is the most common extra-cranial embryonal tumour in children. Treatment outcomes and five-year survival rates are very poor, thus for improved results there is a need to understand its genetic and molecular drivers. Aim: This laboratory project focused on novel genes that can potentially be targeted to induce growth sup- pression or increase neural differentiation in neuroblastoma cells. To characterise the novel growth-promoting or suppressive actions of selected oxovanadium-response genes, coded BRG1-5, and putative suppressor gene PTPRH, through gain/loss-of-function assays and enzyme inhibitory assays in neuroblastoma cells.

Methods: SiRNA and plasmid of the genes were transfected into neuroblastoma cells; Cell morphology was studied by microscopy, and quantitation of growth was done through resazurin assays. Inhibitors of glycosaminoglycan synthesis, thought to be upstream of BRG3, were assayed using resazurin to check the involvement of glycosaminoglycan signaling in NB cell survival.

Conclusion: This study identified the growth-promoting and suppressing effects of the novel genes in Neuroblastoma and confirmed the morphological location of the proteins in some neuroblastoma cell lines.  In addition, it estimated the response to Glycosaminoglycan synthesis inhibitor and calculated the EC50. This Glycosaminoglycan pathway, potentially acting via BRG3, could present a route for defining a new target treatment for Neuroblastoma. The novel BRG3 data may be of particular interest, since BRG3 is implicated in other cancers, but not so far in neuroblastoma.

Author(s): Dalia Hammouche

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