Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied.
Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma.
Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1.
Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.
Keywords: Cell proliferation; DDIAS; Glioma; LEF1; Stemness.
Copyright 2024, Chen et al.