胶质母细胞瘤是一种致命的肿瘤，其胶质母细胞瘤干细胞群参与替莫唑胺（TMZ）耐药。为了深入了解自我更新和耐药性癌症干细胞的机制，利用亚细胞蛋白质组学来鉴定在 U251 衍生的胶质母细胞瘤干细胞样细胞中表达丰富的蛋白质。与分化的衍生物相比，包含 KH RNA 结合域、信号转导相关 3 (KHDRBS3) 的 KHDRBS3 被成功鉴定为癌症干细胞群中上调的基因。通过 RNA 沉默来消除 KHDRBS3 会导致细胞增殖、神经球形成、迁移和与胶质母细胞瘤干性相关的基因表达减少。重要的是，TMZ 敏感性可以通过基因敲低来诱导。总的来说，我们的结果强调 KHDRBS3 是与胶质母细胞瘤干细胞样细胞自我更新和 TMZ 耐药性相关的新因子。因此，靶向 KHDRBS3 可能有助于根除胶质母细胞瘤干细胞样细胞。版权所有 © 2024 Elsevier Inc. 保留所有权利。

Glioblastoma is a deadly tumor which possesses glioblastoma stem cell populations involved in temozolomide (TMZ) resistance. To gain insight into the mechanisms of self-renewing and therapy-resistant cancer stem cells, subcellular proteomics was utilized to identify proteins whose expression is enriched in U251-derived glioblastoma stem-like cells. The KH RNA Binding Domain Containing, Signal Transduction Associated 3, KHDRBS3, was successfully identified as a gene up-regulated in the cancer stem cell population compared with its differentiated derivatives. Depletion of KHDRBS3 by RNA silencing led to a decrease in cell proliferation, neurosphere formation, migration, and expression of genes involved in glioblastoma stemness. Importantly, TMZ sensitivity can be induced by the gene knockdown. Collectively, our results highlight KHDRBS3 as a novel factor associated with self-renewal of glioblastoma stem-like cells and TMZ resistance. As a consequence, targeting KHDRBS3 may help eradicate glioblastoma stem-like cells.Copyright © 2024 Elsevier Inc. All rights reserved.