这篇文章研究了转录因子OTX2在恶性小儿脑瘤3组髓母细胞瘤 (MB) 中的非经典作用。研究发现，OTX2通过蛋白质相互作用与剪接调节复合物（LASR）结合，调节一种干细胞剪接程序，从而促进肿瘤进展。具体而言，OTX2调节替代剪接事件，特别是早期谱系基因 PPHLN1 和晚期谱系基因 MADD 的剪接变体，这些变体与肿瘤的干细胞状态和恶性亚型相关。实验结果表明，靶向 PPHLN1 剪接可以抑制体外肿瘤球生长并延长体内小鼠的生存期，这表明 OTX2 介导的替代剪接是潜在的治疗靶点。References: Saulnier O, Zagozewski J, Liang L, et al. A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing[J]. Nature Cell Biology, 2024, 26(8): 1233-1246.
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