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甲状腺激素的稳态状况与脑水运动作为脑胶质瘤生物学中的决定因素:一项采用生物信息学方法的初步研究

Homeostatic status of thyroid hormones and brain water movement as determinant factors in biology of cerebral gliomas: a pilot study using a bioinformatics approach.

作者信息

Mendes Carmelita Bastos, da Rocha Lanni Sarmento, de Carvalho Fraga Carlos Alberto, Ximenes-da-Silva Adriana

机构信息

Laboratório de Eletrofisiologia e Metabolismo Cerebral, Instituto de Ciências Biológicas e da Saúde, Universidade Federal de Alagoas, Maceió, Brazil.

Faculdade de Medicina, Universidade Federal de Alagoas, Arapiraca, Brazil.

出版信息

Front Neurosci. 2024 Feb 27;18:1349421. doi: 10.3389/fnins.2024.1349421. eCollection 2024.

Abstract

INTRODUCTION

The expression and localization of the water channel transporters, aquaporins (AQPs), in the brain are substantially modified in gliomas during tumorigenesis, cell migration, edema formation, and resolution. We hypothesized that the molecular changes associated with AQP1 and AQP4 in the brain may potentially be anticancer therapeutic targets. To test this hypothesis, a bioinformatics analysis of publicly available data from international consortia was performed.

METHODS

We used RNA-seq as an experimental strategy and identified the number of differential and transcript expressions in glioma tissue compared to normal brain tissue.

RESULTS

AQPs genes are overexpressed in patients with glioma. Among the glioma subtypes, AQP1 and AQP4 were overexpressed in astrocytoma (low-grade glioma) and classical (high-grade glioma). Overall survival analysis demonstrated that both AQP genes can be used as prognostic factors for patients with low-grade glioma. Additionally, we observed a correlation between the expression of genes involved in the tyrosine and thyroid hormone pathways and AQPs, namely: , and (Spearman's coefficient = 0.20 and -value = ≤ 0.05).

CONCLUSION

Our findings indicate that the thyroid hormone pathways and AQPs 1 and 4 are potential targets for new anti-tumor drugs and therapeutic biomarkers for malignant gliomas.

摘要

引言

在脑肿瘤发生、细胞迁移、水肿形成及消退过程中,水通道转运蛋白水通道蛋白(AQPs)在脑内的表达和定位在胶质瘤中发生了显著改变。我们推测,脑内与水通道蛋白1(AQP1)和水通道蛋白4(AQP4)相关的分子变化可能是潜在的抗癌治疗靶点。为验证这一假设,我们对来自国际联盟的公开可用数据进行了生物信息学分析。

方法

我们采用RNA测序作为实验策略,确定了胶质瘤组织与正常脑组织中差异表达和转录本表达的数量。

结果

水通道蛋白基因在胶质瘤患者中过表达。在胶质瘤亚型中,AQP1和AQP4在星形细胞瘤(低级别胶质瘤)和经典型(高级别胶质瘤)中过表达。总体生存分析表明,这两个水通道蛋白基因均可作为低级别胶质瘤患者的预后因素。此外,我们观察到参与酪氨酸和甲状腺激素途径的基因表达与水通道蛋白之间存在相关性,即: ,以及 (斯皮尔曼系数 = 0.20, 值 = ≤ 0.05)。

结论

我们的研究结果表明,甲状腺激素途径以及水通道蛋白1和4是恶性胶质瘤新的抗肿瘤药物和治疗生物标志物的潜在靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1b5b/10927765/a2b0107d06ba/fnins-18-1349421-g001.jpg

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