神经管缺损和胶质母细胞瘤相关基因。

IF 3.9 2区 综合性期刊 Q1 MULTIDISCIPLINARY SCIENCES
Rui Cao, Yurong Liu, Kaixin Wei, Ning Jin, Yuxiang Liang, Ruifang Ao, Weiwei Pan, Xiang Wang, Xiuwei Wang, Li Zhang, Jun Xie
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引用次数: 0

摘要

早期胚胎发育和肿瘤发生有许多相似之处。神经管缺损(NTDs)和胶质母细胞瘤(GBM)的发生都与神经外胚层细胞的异常发育有关。获得与ntd和GBM相关的基因,以及具有潜在临床应用价值的小分子药物。我们对维甲酸(RA)诱导的NTDs小鼠、人类NTDs样本和GBM样本的转录组测序数据进行了生物信息学分析。采用RT-qPCR、Western blot、免疫组化等方法验证候选基因的表达。我们的研究结果表明,在NTDs小鼠和GBM人类样本中,有两个基因在mRNA和蛋白水平上得到了很好的验证,即Poli和Fgf1。使用Autodock和Biacore进行FGF1对抗pazopanib的分子对接和体外验证。细胞学实验表明,pazopanib显著抑制GBM肿瘤细胞和小鼠神经细胞的增殖,促进细胞凋亡,对GBM肿瘤细胞迁移无影响。总之,我们的研究结果表明Fgf1在不同的发育阶段异常表达,它可能是NTDs的潜在产前生物标志物和GBM的潜在治疗靶点。帕唑帕尼有望成为治疗GBM肿瘤的新药。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Genes related to neural tube defects and glioblastoma.

There are many similarities between early embryonic development and tumorigenesis. The occurrence of neural tube defects (NTDs) and glioblastoma (GBM) are both related to the abnormal development of neuroectodermal cells. To obtain genes related to both NTDs and GBM, as well as small molecule drugs with potential clinical application value. We performed bioinformatics analysis on transcriptome sequencing data of retinoic acid (RA)-induced NTDs mice, human NTDs samples and GBM samples. RT-qPCR, Western blot, and immunohistochemistry were used to validate the expression of candidate genes. Our results indicated that two genes at mRNA and protein levels have been well verified in both NTDs mouse and GBM human samples, namely, Poli and Fgf1. Molecular docking and validating in vitro were performed for FGF1 against pazopanib by using Autodock and Biacore. Cytological experiments showed that pazopanib significantly inhibited the proliferation of GBM tumor cells and mouse neural cells, promoted apoptosis, and had no effect on GBM tumor cells migration. Overall, our results demonstrated that Fgf1 abnormally expressed at different developmental stages, it may be a potentially prenatal biomarker for NTDs and potential therapeutic target for GBM. Pazopanib may be a new drug for the treatment of GBM tumors.

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来源期刊
Scientific Reports
Scientific Reports Natural Science Disciplines-
CiteScore
7.50
自引率
4.30%
发文量
19567
审稿时长
3.9 months
期刊介绍: We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections. Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021). •Engineering Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live. •Physical sciences Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics. •Earth and environmental sciences Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems. •Biological sciences Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants. •Health sciences The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
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