SUV39H1 regulates progression of pediatric diffuse high-grade gliomas through modulation of β-catenin/TCF4 levels

Background Pediatric high-grade gliomas (pHGGs) are heterogeneous, diffuse, and infiltrative tumors with dismal prognosis. Recent molecular characterization of pHGGs has revealed aberrant post-translational histone modifications with elevated histone 3 lysine trimethylation (H3K9) to be implicated in their pathology. Herein, we investigate the biological role of suppressor of variegation 3–9 homolog 1 (SUV39H1) methyltransferase in cell proliferation, motility, and gene regulation of pHGG. Methods SUV39H1 mRNA levels were first determined in a public database of pediatric gliomas and respective controls. SUV39H1 protein levels were further investigated in a cohort of 24 pHGG tissues and respective controls by immunohistochemistry and western immunoblotting. Gene silencing of SUV39H1 was performed in pHGG cell lines (SJ-GBM2 and CHLA-200) to investigate their functional role in cell proliferation, migration, adhesion and epithelial-mesenchymal transition (EMT) markers. Results SUV39H1 mRNA was found enriched in pHGG compared to normal brain with KEGG pathway analysis revealing a positive correlation with cell adhesion molecules. Further immunohistochemical analysis of a cohort of pHGG detected significantly increased SUV39H1 protein expression in pHGG tissues followed by elevated H3K9me3 expression compared to normal brain tissues. Gene silencing of SUV39H1 in patient-derived pHGG cell lines, SJGBM2 and CHLA-200 showed a significant reduction in cell viability and cell migration followed by decreased expression of vimentin, β-catenin and TCF4 protein levels. Furthermore, SUV39H1 silencing reduced the mRNA levels of EMT marker genes CDH2 , SNAI1 and MARCKS . Conclusion Our findings demonstrate that SUV39H1 regulates cell proliferation and adhesion in pHGG, contributing to epithelial-mesenchymal transition and presenting a promising therapeutic target to be investigated further.