P02.10.A CRISPR/Cas9 deletion of SOX2 Regulatory Region 2 (SRR2) decreases SOX2 malignant activity in glioblastoma

Abstract Background SOX2 is a transcription factor associated with stem cell activity in several tissues. expression elevated large proportion of cancers, such as glioblastoma (GB), the most common malignant primary brain tumor adults. acts relevant driver GB progression and high levels are population initiating cells poor patient outcome. Transcriptional regulation complex not fully understood. The regulatory region 2 (SRR2) located downstream coding mediates by association p21CIP1 p27KIP1 to SRR2. In this study we dissected role SRR2 on GB. Material Methods We deleted (SRR2del) CRISPR/Cas9 technology U373 cells. analyzed performed vitro functional experiments. accomplished rescue experiments overexpressing SRR2del studied link between SOX2, p27KIP1. Finally, carried out an vivo carcinogenesis assay injection immunodeficient mice. Results report that deletion leads reduction expression, which was accompanied impairment growth proliferation well self-renewal capacity vitro. These data reveal required for its results impaired tumorigenic effects correlated increased together p53 On contrary, presented decreased markers, supporting idea necessary SOX2-mediated stemness pathways. Furthermore, ectopic overexpression restored properties, indicating oncogenic regulated Additionally, our xenograft models revealed lack impairs initiation vivo. Tumors derived from were significantly smaller compared controls exhibit low Ki67 BMI1 but Conclusion Our confirm regulates reduces halts driven