PLEKHA4 promotes glioblastoma progression through apoptosis inhibition, tumor cell migration, and macrophage infiltration

IF 4.6 Q2 MATERIALS SCIENCE, BIOMATERIALS ACS Applied Bio Materials Pub Date : 2023-11-01 DOI:10.1016/j.imbio.2023.152746

Yang He , Wenjing Zheng , Yi Huo , Longqi Sa , Han Zhang , Guangbin He , Panfeng Shang

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Abstract

Background

Glioblastoma(GBM) has a profound impact on human health, making the identification of reliable prognostic biomarkers pivotal. While PLEKHA4 has been associated with tumor genesis and development, its role in gliomas is still uncertain.

Methods

We analyzed PLEKHA4 expression in tumor tissues using the Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. Additionally, we utilized TCGA data to investigate its impact on prognosis, pathway enrichment, and immune infiltration. In vitro loss-of-function experiments were conducted to elucidate the effect of PLEKHA4 silencing on GBM cell behavior.

Results

TCGA and GEO data sets revealed increased levels of PLEKHA4 expression in glioma tissues. Furthermore, we identified a correlation between PLEKHA4 expression and higher disease classification, pathological grading, and poorer prognosis. Silencing PLEKHA4 in vitro resulted in decreased glioma cell migration and increased apoptosis. It also reduced macrophage infiltration and hindered M2 polarization of macrophages.

Conclusion

Our findings highlight the pivotal role of PLEKHA4 in GBM pathogenesis and suggest its potential as a diagnostic and therapeutic target for GBM.

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PLEKHA4通过抑制细胞凋亡、肿瘤细胞迁移和巨噬细胞浸润来促进胶质母细胞瘤的进展

胶质母细胞瘤(GBM)对人类健康有着深远的影响，因此确定可靠的预后生物标志物至关重要。虽然PLEKHA4与肿瘤的发生和发展有关，但其在胶质瘤中的作用仍不确定。方法利用肿瘤基因组图谱(Cancer Genome Atlas, TCGA)和基因表达图谱(Gene expression Omnibus, GEO)数据库分析PLEKHA4在肿瘤组织中的表达。此外，我们利用TCGA数据研究其对预后、通路富集和免疫浸润的影响。通过体外功能丧失实验来阐明PLEKHA4沉默对GBM细胞行为的影响。结果stcga和GEO数据集显示PLEKHA4在胶质瘤组织中的表达水平升高。此外，我们发现PLEKHA4表达与较高的疾病分类、病理分级和较差的预后之间存在相关性。体外沉默PLEKHA4导致胶质瘤细胞迁移减少，细胞凋亡增加。减少巨噬细胞浸润，抑制巨噬细胞M2极化。结论PLEKHA4在GBM发病机制中的关键作用，提示其可能作为GBM的诊断和治疗靶点。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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