鉴定 PDLIM1 为胶质母细胞瘤干细胞标记物，可驱动肿瘤发生和化疗抗药性。

IF 6.1 2区生物学 Q1 CELL BIOLOGY

Cell Death Discovery Pub Date : 2024-11-15 DOI:10.1038/s41420-024-02241-7

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

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引用次数: 0

摘要

胶质母细胞瘤（GBM）是一种侵袭性脑肿瘤，预后较差，这主要是由于胶质母细胞瘤干细胞（GSC）的存在。这些细胞驱动肿瘤进展、复发和化疗耐药性，使其成为治疗的关键靶点。本研究旨在鉴定新型GSC标记物，以改进诊断和靶向治疗。我们利用单细胞RNA测序（scRNA-seq）和大量RNA-seq数据确定了PDLIM1作为新型GSC标记物。PDLIM1在GSC中特异性表达，与预后不良和肿瘤晚期有关。功能测试表明，PDLIM1过表达会增强GBM细胞增殖，减少细胞凋亡，增加GSC比例，促进化疗耐受性和肿瘤发生。相反，PDLIM1 基因敲除则会抑制这些过程。从机理上讲，PDLIM1 可能是通过促进 PI3K-AKT 通路来发挥其作用的。总之，PDLIM1 可作为与 GBM 预后不良、肿瘤发生和化疗耐药相关的 GSC 的潜在标志物，是改善 GBM 患者预后的潜在治疗靶点。

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

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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来源期刊

Cell Death Discovery Biochemistry, Genetics and Molecular Biology-Cell Biology

CiteScore

8.30

自引率

1.40%

发文量

468

审稿时长

9 weeks

期刊介绍： Cell Death Discovery is a multidisciplinary, international, online-only, open access journal, dedicated to publishing research at the intersection of medicine with biochemistry, pharmacology, immunology, cell biology and cell death, provided it is scientifically sound. The unrestricted access to research findings in Cell Death Discovery will foster a dynamic and highly productive dialogue between basic scientists and clinicians, as well as researchers in industry with a focus on cancer, neurobiology and inflammation research. As an official journal of the Cell Death Differentiation Association (ADMC), Cell Death Discovery will build upon the success of Cell Death & Differentiation and Cell Death & Disease in publishing important peer-reviewed original research, timely reviews and editorial commentary. Cell Death Discovery is committed to increasing the reproducibility of research. To this end, in conjunction with its sister journals Cell Death & Differentiation and Cell Death & Disease, Cell Death Discovery provides a unique forum for scientists as well as clinicians and members of the pharmaceutical and biotechnical industry. It is committed to the rapid publication of high quality original papers that relate to these subjects, together with topical, usually solicited, reviews, editorial correspondence and occasional commentaries on controversial and scientifically informative issues.