Shi Zhongju, Wei Zhijian, Li Jiahe, Yuan Shiyang, Pan Bin, Cao Fujiang, Zhou Hengxing, Zhang Yan, Wang Yao, Sun Shiwei, Kong Xiaohong, Feng Shiqing
Department of Orthopaedics, Tianjin Medical University General Hospital, Tianjin, China.
Department of Orthopaedics, The Affiliated Hospital of Xuzhou Medical University, Xuzhou, China.
Cell Physiol Biochem. 2018;47(1):212-222. doi: 10.1159/000489799. Epub 2018 May 10.
BACKGROUND/AIMS: Neural stem cells (NSCs) reside in a hypoxic environment, and hypoxia plays an important role in their development and differentiation. This study aimed to explore the underlying mechanisms by which hypoxia affects NSC behavior.
In the current study, we downloaded the gene expression dataset GSE68572 and identified the differentially expressed genes (DEGs) by analyzing high-throughput gene expression in hypoxic and normoxic NSCs. Subsequently, we analyzed these data using a combined bioinformatics approach and predicted the microRNAs (miRNAs) targeting the key gene using miRNA databases. Quantitative real-time PCR (qRT-PCR) was used to validate the expression of the top five DEGs.
In total, 1347 genes were identified as DEGs. We identified the predominant gene ontology categories and Kyoto Encyclopedia of Genes and Genomes pathways that were significantly over-represented in the hypoxic NSCs. A protein-protein interaction network he identification of miRNAs and their putative targets may offer new diagnostic and therapeutic strategies for liver cancer the top 10 core genes. Vascular endothelial growth factor A (VEGFA) had the highest degree and may be the key gene concerning NSC behavior under hypoxia. Further validation of the top five DEGs by qRT-PCR demonstrated that four DEGs were significantly higher and one DEG was significantly lower in the hypoxic group than in the control group. Seven miRNAs were predicted and proved to target VEGFA.
This preliminary study can prompt the understanding of the molecular mechanisms by which hypoxia has an impact on NSC behavior and can help to optimize stem cell therapies for central nervous system injuries and diseases.
背景/目的：神经干细胞（NSCs）存在于低氧环境中，低氧在其发育和分化中起重要作用。本研究旨在探讨低氧影响神经干细胞行为的潜在机制。
在本研究中，我们下载了基因表达数据集GSE68572，并通过分析低氧和常氧神经干细胞中的高通量基因表达来鉴定差异表达基因（DEGs）。随后，我们使用联合生物信息学方法分析这些数据，并使用miRNA数据库预测靶向关键基因的微小RNA（miRNAs）。采用定量实时PCR（qRT-PCR）验证排名前五的DEGs的表达。
共鉴定出1347个DEGs。我们确定了在低氧神经干细胞中显著富集的主要基因本体类别和京都基因与基因组百科全书通路。一个蛋白质-蛋白质相互作用网络 对miRNAs及其推定靶点的鉴定可能为肝癌提供新的诊断和治疗策略 排名前10的核心基因。血管内皮生长因子A（VEGFA）的连接度最高，可能是低氧条件下与神经干细胞行为相关的关键基因。通过qRT-PCR对排名前五的DEGs进行进一步验证，结果显示低氧组中有四个DEGs显著高于对照组，一个DEG显著低于对照组。预测并证实有7种miRNAs靶向VEGFA。
这项初步研究可以促进对低氧影响神经干细胞行为的分子机制的理解，并有助于优化针对中枢神经系统损伤和疾病的干细胞治疗。
