PO.BCS01.13 · 生物信息与计算
研究保守的 Notch 通路在胶质母细胞瘤细胞中的作用
Investigating the role of the conserved notch pathway in glioblastoma cells
作者与单位 Authors & Affiliations
摘要 Abstract
中文摘要
胶质母细胞瘤（GBM）仍然是最具侵袭性的原发性脑癌，占所有脑部恶性肿瘤的近 50%，中位生存期不足 15 个月。我们实验室已发现 FOXO4 转录因子在维持 GBM 干细胞样表型中的作用。为进一步研究这一新作用，我们对实验室使用 CRISPR Cas9 诱变生成的 FOXO4 敲除 U87MG 细胞进行了 RNA 测序。我们发现，U87MG 细胞系中 FOXO4 的缺失改变了 NOTCH3 及其下游靶标（如 CCND1）的表达。此外，外源性 NOTCH3 在 U87MG 细胞中诱导了 CCND1 的表达。这些初步发现提示，FOXO4 的转录活性可能至少部分通过调节 NOTCH3 的激活来影响胶质母细胞瘤的侵袭性。正在进行的研究旨在确认 FOXO4-NOTCH3 轴对于维持 GBM 细胞的干细胞样状态是否必不可少。阐明这一相互作用可能揭示新的治疗干预分子靶点，并推进我们对 GBM 发病机制的理解。
查看英文原文 English abstract
Glioblastoma (GBM) remains the most aggressive primary brain cancer, representing nearly 50% of all brain malignancies, with a median survival of less than 15 months. Our lab has identified a role for the FOXO4 transcription factor in maintaining a stem-like phenotype in GBM. To further investigate this novel role, we performed RNA sequencing on FOXO4 knockout U87MG cells generated in our laboratory using CRISPR Cas9 mutagenesis. We found that loss of FOXO4 in U87MG cell lines altered the expression of NOTCH3 and its downstream targets, such as CCND1 . Furthermore, exogenous NOTCH3 induced CCND1 expression in U87MG cells. These preliminary findings suggest that FOXO4 transcriptional activity may influence glioblastoma aggressiveness at least in part by modulation of NOTCH3 activation. Ongoing studies aim to confirm whether the FOXO4-NOTCH3 axis is essential for maintaining stem-like states in GBM cells. Elucidating this interaction could uncover novel molecular targets for therapeutic intervention and advance our understanding of GBM pathogenesis.
利益披露 Disclosure
L. Barroso, None..
M. E. Keniry, None.