Identification of PDLIM1 as a glioblastoma stem cell marker driving tumorigenesis and chemoresistance

鉴定出 PDLIM1 是驱动肿瘤发生和化学耐药性的胶质母细胞瘤干细胞标志物

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作者:Xiaopeng Shen #, Yun Zhao #, Yang Cao #, Yunfeng Liu #, Jian Ruan #, Chunguang Wang, Meng Li, Huaizhang Jin, Shan Lu, Guoping Zhu

Abstract

Glioblastoma (GBM) is an aggressive brain tumor with a poor prognosis, largely due to the presence of glioblastoma stem cells (GSCs). These cells drive tumor progression, recurrence, and chemoresistance, making them critical targets for therapy. This study aims to identify novel GSC markers for improved diagnosis and targeted treatment. We utilized single-cell RNA sequencing (scRNA-seq) and bulk RNA-seq data to identify PDLIM1 as a novel GSC marker. PDLIM1 was specifically expressed in GSCs and was associated with poor prognosis and advanced tumor stages. Functional assays demonstrated that PDLIM1 overexpression enhanced GBM cell proliferation, reduced apoptosis, increased GSC proportions, and promoted chemoresistance and tumorigenesis. Conversely, PDLIM1 knockdown inhibited these processes. Mechanistically, PDLIM1 was found to exert its effects likely by promoting the PI3K-AKT pathway. In conclusion, PDLIM1 may serve as a potential marker of GSCs associated with poor prognosis, tumorigenesis, and chemoresistance in GBM, representing a potential therapeutic target for improving GBM patient outcomes.

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