Therapeutic implications of endoplasmic reticulum stress gene CCL3 in cervical squamous cell carcinoma.

IF 5.9 2区 医学 Q2 CELL BIOLOGY
Yingping Zhu, Wei Xu, Yuanfang He, Wenjuan Yang, Siyue Song, Chengping Wen
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引用次数: 0

Abstract

This study investigated ERS-related gene expressions in CESC, identifying two molecular subtypes, P1 and P2, and constructing a precise prognostic model based on these subtypes. TCGA's whole-genome expression profiles were used to recognize these subtypes through the ConsensusClusterPlus method, further refining prognostic models with univariate and Lasso Cox regression analyses validated by the GSE39001 dataset. The study analyzed the expression distribution of ERS marker genes within T cell subgroups using scRNA-seq data (GSE168652), highlighting T cell diversity. The critical role of the CCL3 gene in prognostic models was examined explicitly in CD8 + T cells from healthy individuals and CESC patients. Elevated CCL3 levels were observed in patients' CD8 + T cells compared to healthy controls. Functional experiments involving CCL3 knockdown and overexpression in HeLa and SiHa CESC cell lines were conducted to investigate its impact on cell proliferation, migration, and invasion. These findings were subsequently validated in a nude mouse model. The results demonstrated that suppressing CCL3 inhibited cell proliferation, migration, and invasion significantly, while its overexpression promoted these processes. In the mouse model, CCL3 silencing reduced tumor growth and decreased Ki-67 labeling within the tumor tissues, indicating the therapeutic potential of targeting CCL3 in CESC treatment, possibly through CD8 + T cell regulation. This study contributes new prognostic assessment tools and personalized treatment options for CESC patients, paving the way for more targeted therapies in CESC by discovering the CCL3 gene, presenting significant clinical implications.

内质网应激基因CCL3在宫颈鳞状细胞癌中的治疗意义。
本研究通过研究ers相关基因在CESC中的表达,确定了P1和P2两种分子亚型,并基于这些亚型构建了精确的预后模型。TCGA的全基因组表达谱通过ConsensusClusterPlus方法识别这些亚型,并通过GSE39001数据集验证的单变量和Lasso Cox回归分析进一步完善预后模型。本研究利用scRNA-seq数据(GSE168652)分析了ERS标记基因在T细胞亚群中的表达分布,突出了T细胞的多样性。在健康个体和CESC患者的CD8 + T细胞中明确检测了CCL3基因在预后模型中的关键作用。与健康对照组相比,在患者的CD8 + T细胞中观察到CCL3水平升高。在HeLa和SiHa CESC细胞系中进行CCL3敲低和过表达的功能实验,研究其对细胞增殖、迁移和侵袭的影响。这些发现随后在裸鼠模型中得到了验证。结果表明,抑制CCL3可显著抑制细胞增殖、迁移和侵袭,而过表达CCL3可促进这些过程。在小鼠模型中,CCL3沉默可降低肿瘤生长并降低肿瘤组织内Ki-67标记,表明靶向CCL3在CESC治疗中的治疗潜力,可能通过CD8 + T细胞调节。本研究为CESC患者提供了新的预后评估工具和个性化治疗方案,通过发现CCL3基因,为CESC更有针对性的治疗铺平了道路,具有重要的临床意义。
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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来源期刊
Cell Biology and Toxicology
Cell Biology and Toxicology 生物-毒理学
CiteScore
9.90
自引率
4.90%
发文量
101
审稿时长
>12 weeks
期刊介绍: Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.
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