Shen Xiaopeng, Zhao Yun, Cao Yang, Liu Yunfeng, Ruan Jian, Wang Chunguang, Li Meng, Jin Huaizhang, Lu Shan, Zhu Guoping
College of Life Sciences, Anhui Normal University, Wuhu, Anhui, China.
Center of Reproductive Medicine, Yijishan Hospital of Wannan Medical College, Wuhu, Anhui, China.
Cell Death Discov. 2024 Nov 15;10(1):469. doi: 10.1038/s41420-024-02241-7.
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.
胶质母细胞瘤(GBM)是一种侵袭性脑肿瘤,预后较差,这在很大程度上归因于胶质母细胞瘤干细胞(GSC)的存在。这些细胞推动肿瘤进展、复发和化疗耐药,使其成为治疗的关键靶点。本研究旨在鉴定新型GSC标志物,以改善诊断和靶向治疗。我们利用单细胞RNA测序(scRNA-seq)和批量RNA-seq数据,将PDLIM1鉴定为一种新型GSC标志物。PDLIM1在GSC中特异性表达,与预后不良和肿瘤晚期相关。功能分析表明,PDLIM1过表达增强了GBM细胞增殖,减少了细胞凋亡,增加了GSC比例,并促进了化疗耐药和肿瘤发生。相反,PDLIM1基因敲低抑制了这些过程。从机制上讲,发现PDLIM1可能通过促进PI3K-AKT信号通路发挥其作用。总之,PDLIM1可能作为与GBM预后不良、肿瘤发生和化疗耐药相关的GSC潜在标志物,代表改善GBM患者预后的潜在治疗靶点。