RUNX1-PDIA5 Axis Promotes Malignant Progression of Glioblastoma by Regulating CCAR1 Protein Expression.

IF 8.2 2区 生物学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY International Journal of Biological Sciences Pub Date : 2024-08-12 eCollection Date: 2024-01-01 DOI:10.7150/ijbs.92595
Qiankun Ji, Zewei Tu, Junzhe Liu, Zhihong Zhou, Fengze Li, Xingen Zhu, Kai Huang
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Abstract

PDIA5 is responsible for modification of disulfide bonds of proteins. However, its impact on the malignant progression of glioblastoma multiforme (GBM) remains unknown. We analyzed the expression and prognostic significance of PDIA5 in cohorts of GBM and clinical samples. The PDIA5 protein was significantly overexpressed in GBM tissues, and higher expression of PDIA5 was statistically associated with a worse prognosis in patients with GBM. Transcriptional data from PDIA5 knockdown GBM cells revealed that downstream regulatory genes of PDIA5 were enriched in malignant regulatory pathways and PDIA5 enhanced the proliferative and invasive abilities of GBM cells. By constructing a PDIA5 CXXC motif mutant plasmid, we found CCAR1 was the vital downstream factor of PDIA5 in regulating GBM malignancy in vitro and in vivo. Additionally, RUNX1 bound to the promoter region of PDIA5 and regulated gene transcription, leading to activation of the PDIA5/CCAR1 regulatory axis in GBM. The RUNX1/PDIA5/CCAR1 axis significantly influenced the malignant behavior of GBM cells. In conclusion, this study comprehensively elucidates the crucial role of PDIA5 in the malignant progression of GBM. Downregulating PDIA5 can mitigate the malignant biological behavior of GBM both in vitro and in vivo, potentially improving the efficacy of treatment for clinical patients with GBM.

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RUNX1-PDIA5轴通过调控CCAR1蛋白表达促进胶质母细胞瘤恶性进展
PDIA5 负责修饰蛋白质的二硫键。然而,它对多形性胶质母细胞瘤(GBM)恶性进展的影响仍然未知。我们分析了 PDIA5 在成组 GBM 和临床样本中的表达和预后意义。PDIA5蛋白在GBM组织中明显过表达,而且据统计,PDIA5的高表达与GBM患者较差的预后有关。PDIA5敲除GBM细胞的转录数据显示,PDIA5的下游调控基因富集在恶性调控通路中,PDIA5增强了GBM细胞的增殖和侵袭能力。通过构建 PDIA5 CXXC 突变质粒,我们发现 CCAR1 是 PDIA5 在体外和体内调控 GBM 恶性的重要下游因子。此外,RUNX1与PDIA5的启动子区域结合并调控基因转录,导致PDIA5/CCAR1调控轴在GBM中被激活。RUNX1/PDIA5/CCAR1 轴显著影响了 GBM 细胞的恶性行为。总之,本研究全面阐明了 PDIA5 在 GBM 恶性进展中的关键作用。下调 PDIA5 可以减轻 GBM 在体外和体内的恶性生物学行为,从而提高临床 GBM 患者的治疗效果。
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来源期刊
International Journal of Biological Sciences
International Journal of Biological Sciences 生物-生化与分子生物学
CiteScore
16.90
自引率
1.10%
发文量
413
审稿时长
1 months
期刊介绍: The International Journal of Biological Sciences is a peer-reviewed, open-access scientific journal published by Ivyspring International Publisher. It dedicates itself to publishing original articles, reviews, and short research communications across all domains of biological sciences.
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