CRNDE,一种在胶质瘤中具有预后价值的增强RNA,与免疫浸润相关:一项泛癌症分析

Pub Date : 2023-03-22 DOI:10.1177/1721727x221138068
Zheng Huo, Lishuo Guo, Weimin Shao, Qian Ding, Yuehong Guo, Qian Xu
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引用次数: 0

摘要

背景:最近有证据表明,增强子RNA (eRNA)结肠直肠癌差异表达(CRNDE)与癌症患者预后之间的关系发生了改变。然而,CRNDE在泛癌症和肿瘤免疫微环境(TIME)中的作用在很大程度上仍未被探索。方法:基于公共数据库,采用多种生物信息学方法,从表达模式、预后、肿瘤免疫、CRNDE与其靶基因IRX5的关联等方面,揭示elncRNA CRNDE在多种癌症中的作用。通过对独立因素进行积分,形成了一个nomogram。基因集富集分析(GSEA)用于确定潜在的信号通路机制。分子生物学实验包括RT-qPCR、MTT、Transwell和伤口愈合分析,以评估胶质瘤细胞的增殖、迁移和侵袭。最后采用RT-qPCR和免疫组织化学方法分析CRNDE在不同级别胶质瘤中的表达和功能。采用尼氏染色法评价CRNDE下调对胶质母细胞瘤组织的潜在影响。结果:在33种癌症类型中的15种中,CRNDE出现异常并与临床特征相关。生存分析显示,高CRNDE表达可能导致6种癌症类型预后恶化。CRNDE可能参与多种癌症类型的免疫调节。CRNDE与多种肿瘤和免疫相关途径相关。此外,CRNDE敲低可抑制胶质瘤细胞的增殖、迁移和侵袭。尼氏染色证实CRNDE siRNA显著抑制肿瘤生长。在低级别胶质瘤中,免疫细胞与CRNDE/IRX5之间的相关性比在胶质母细胞瘤多形性组织中更强,并且与IRX5和免疫检查点基因NRP1之间存在关联。结论:增强子RNA CRNDE可作为肿瘤免疫浸润及预后不良的生物标志物,为肿瘤治疗提供新的途径。
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CRNDE, an enhancer RNA of prognostic value in glioma, correlates with immune infiltration: A pan-cancer analysis
Background: Recent evidence has emerged regarding the modification of the relationship between the enhancer RNA (eRNA) colorectal neoplasia differentially expressed (CRNDE) and the prognosis of patients with cancer. Nevertheless, the role of CRNDE in pan-cancer and tumour immune microenvironment (TIME) remains largely unexplored. Methods: Multiple bioinformatic methods were employed to unravel the role of elncRNA CRNDE in a wide range of cancers from the perspective of the expression patterns, prognosis, tumour immunity, and the association between CRNDE and its target gene IRX5 based on the public database. A nomogram was created by integrating independent factors. Gene set enrichment analysis (GSEA) was used to determine the potential signalling pathway mechanisms. Molecular biology experiments including RT-qPCR, MTT, Transwell, and wound-healing analyses were performed to evaluate the proliferation, migration, and invasion of glioma cells. Finally, RT-qPCR and immunohistochemistry were performed to analyse the expression and function of CRNDE in gliomas of different grades. Nissl staining was used to evaluate the potential effects of CRNDE knockdown in glioblastoma tissues. Results: CRNDE was dysregulated and associated with clinical features in 15 of the 33 cancer types. The survival analysis showed that high CRNDE expression might lead to a worsened prognosis among the six cancer types. CRNDE might be involved in immune regulation in multiple cancer types. CRNDE correlated with multiple tumours and immune-related pathways. Additionally, CRNDE knockdown inhibited glioma cell proliferation, migration, and invasion. Nissl staining confirmed that CRNDE siRNA notably decreased tumour growth. A stronger correlation between immune cells and CRNDE/IRX5 in lower-grade glioma than in glioblastoma multiforme tissues, and an association with IRX5 and immune checkpoint gene NRP1 were observed. Conclusions: An Enhancer RNA CRNDE may serve as a biomarker for cancer immunologic infiltration and poor prognosis, providing a new approach for cancer treatment.
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