Prognostic Significance and Functional Mechanism of UTS2 in Glioblastoma Multiforme

IF 2.3 4区医学 Q3 ONCOLOGY

Current cancer drug targets Pub Date : 2024-01-23 DOI:10.2174/0115680096275291231226081320

Yanfei Wang, Langping Shen, Mingzhong Sun

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引用次数: 0

Abstract

Aim: We aimed to explore the role of urotensin 2 (UTS2) in glioblastoma (GBM).

Background: GBM is the most malignant primary brain cancer with a poor prognosis. Previous studies have suggested that GBM vessels undergo dynamic remodeling modulated by tumor vasodilation and vasoconstriction instead of tumor angiogenesis.

Objective: Here, we have first investigated the expression and function of UTS2, a potent vasoconstrictor, in GBM.

Methods: The mRNA expression profiles and clinical information of GBM patients were obtained from the TCGA database. The clinical relevance of UTS2 was explored by the Mann-Whitney U test and Cox hazard regression survival test. We further explored the role of UTS2 in GBM cell proliferation, migration, and tumor immune microenvironment. Moreover, we established the in vivo mice model to validate its oncogenic effects on GBM progression.

Results: Although we did not find significant correlations between UTS2 expression and patients’ clinical characteristics, UTS2 was identified as a valid independent prognostic indicator according to multivariate survival analysis. Knockdown of UTS2 resulted in decreased GBM cell proliferation and migration. In addition, functional enrichment analysis implied UTS2 to be involved in the regulation of the immune microenvironment. In vivo studies showed that UTS2 knockdown suppressed GBM xenograft growth, highlighting the tumor-promoting effects of UTS2 on GBM.

Conclusion: Our study identified that UTS2 could predict the prognosis of GBM patients and provided evidence regarding its oncogenic effects both in vitro and in vivo.

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UTS2在多形性胶质母细胞瘤中的预后意义和功能机制

目的：我们旨在探索尿促性素 2（UTS2）在胶质母细胞瘤（GBM）中的作用：背景：GBM 是恶性程度最高的原发性脑癌，预后较差。以前的研究表明，GBM血管经历了由肿瘤血管扩张和血管收缩而非肿瘤血管生成所调节的动态重塑。目的：在此，我们首次研究了UTS2（一种强效血管收缩因子）在GBM中的表达和功能：方法：从 TCGA 数据库中获取 GBM 患者的 mRNA 表达谱和临床信息。方法：我们从 TCGA 数据库中获取了 GBM 患者的 mRNA 表达谱和临床信息，并通过 Mann-Whitney U 检验和 Cox 危险回归生存检验探讨了 UTS2 的临床相关性。我们进一步探讨了UTS2在GBM细胞增殖、迁移和肿瘤免疫微环境中的作用。此外，我们还建立了体内小鼠模型，以验证UTS2对GBM进展的致癌作用：结果：虽然我们没有发现UTS2的表达与患者的临床特征有明显的相关性，但根据多变量生存分析，UTS2被确定为一个有效的独立预后指标。敲除UTS2可减少GBM细胞的增殖和迁移。此外，功能富集分析表明UTS2参与了免疫微环境的调节。体内研究显示，UTS2敲除抑制了GBM异种移植的生长，突出了UTS2对GBM的肿瘤促进作用：我们的研究发现，UTS2 可以预测 GBM 患者的预后，并提供了其体外和体内致癌作用的证据。

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

Current cancer drug targets 医学-肿瘤学

CiteScore

5.40

自引率

0.00%

发文量

105

审稿时长

1 months

期刊介绍： Current Cancer Drug Targets aims to cover all the latest and outstanding developments on the medicinal chemistry, pharmacology, molecular biology, genomics and biochemistry of contemporary molecular drug targets involved in cancer, e.g. disease specific proteins, receptors, enzymes and genes. Current Cancer Drug Targets publishes original research articles, letters, reviews / mini-reviews, drug clinical trial studies and guest edited thematic issues written by leaders in the field covering a range of current topics on drug targets involved in cancer. As the discovery, identification, characterization and validation of novel human drug targets for anti-cancer drug discovery continues to grow; this journal has become essential reading for all pharmaceutical scientists involved in drug discovery and development.