INVESTIGATING THE ROLE OF FLOTILLIN-1 AND HIGH MOBILITY GROUP BOX 1 IN HISTONE 3 MUTATED PAEDIATRIC HIGH-GRADE GLIOMAS

Abstract AIMS Paediatric gliomas are the most prevalent central nervous system tumours diagnosed between birth and age 19. Gain-of-function mutation in H3 histone tail can contribute to a subset of paediatric high-grade gliomas (pHGGs). Our previous research has shown that the cell membrane topography in pHGG is distinct from normal cells in their expression and localisation of Flotillin-1 and high mobility group box 1 (HMGB1). Flotillin-1 dysregulation is a hallmark of tumorigenesis. HMGB1 is nucleoprotein whose function varies with tumour progression. This study investigated the localisation and expression of Flotillin-1 and HMGB1 in in pHGG in comparison to different controls. METHODS The localisation and expression of Flotillin-1 and HMGB1 was studies with immunofluorescence and western blot experiments using KNS42 (H3-G34V), SF188 (H3-WT), HeLa (control) and Astrocytes (control) cell lines. The quantification of expression was calculated and analysed statistically. RESULTS H3-G34V cells showed significantly higher cell membrane and cytoplasmic localisation for Flotillin 1 and HMGB1, respectively, compared to the H3-WT and control cell lines. The expression of HMGB1 and Flotillin- 1 was highest in H3-G34V cells compared to the H3-WT and control cell lines including astrocytes. CONCLUSION The overexpression of Flotillin-1 and HMGB1 expression are observed in pHGG and are associated with dismal cancer prognosis. Further research is required to study the downstream effects of these pathways to identify target molecules for cancer treatment.