Department of Biochemistry and Molecular Biology, Shanxi Key Laboratory of Birth Defect and Cell Regeneration, Key Laboratory for Cellular Physiology of Ministry of Education, Shanxi Medical University, Taiyuan, Shanxi, China (mainland).
Shanxi Biological Research Institute Co., Ltd., Taiyuan, Shanxi, China (mainland).
Med Sci Monit. 2022 Mar 23;28:e936079. doi: 10.12659/MSM.936079.
BACKGROUND Previous studies have demonstrated that embryo development and the occurrence of tumors are closely related, as key genes, pathways, miRNAs, and other biological mechanisms are involved in both processes. Extensive research has found that abnormal development of nerve ectodermal cells not only leads to neural tube defects (NTDs), but also neuroectodermal tumors. MATERIAL AND METHODS Genes associated with both NTDs and neuroectodermal tumors were obtained from the DisGeNET database. The STRING database was used to construct the protein-protein interaction (PPI) network and the hub genes were visualized using Cytoscape. Additionally, we predicted the miRNAs targeting the identified genes. Sequencing data obtained from an NTDs mouse model and human samples were used to confirm the bioinformatics results. Moreover, a dual-luciferase report assay was used to validate the targeting relationship between the miRNA-gene pairs identified. RESULTS A total of 104 intersection genes of NTDs-related and neuroectodermal tumors-related genes were obtained; 20 of these genes were differentially expressed in NTDs samples and had very close interactions. Among 10 hub genes, we identified 3 important susceptibility genes differentially expressed both in RA-induced NTDs mice and human glioblastoma samples: Ncam1, Shh, and Ascl1. Among these, we found that the Ncam1 expression level was regulated by mmu-miR-30a-5p, and the Ascl1 expression level was regulated by mmu-miR-375-3p. CONCLUSIONS In conclusion, we identified differentially expressed genes and a potential miRNA-mediated regulation mechanism shared between NTDs and neuroectodermal tumors that may guide future studies aiming to find novel therapeutic targets for NTDs or neuroectodermal tumors.
先前的研究表明,胚胎发育和肿瘤的发生密切相关,因为关键基因、途径、miRNA 和其他生物学机制都涉及这两个过程。广泛的研究发现,神经外胚层细胞的异常发育不仅导致神经管缺陷(NTDs),还导致神经外胚层肿瘤。
从 DisGeNET 数据库中获取与 NTDs 和神经外胚层肿瘤都相关的基因。使用 STRING 数据库构建蛋白质-蛋白质相互作用(PPI)网络,并使用 Cytoscape 可视化枢纽基因。此外,我们预测了针对鉴定基因的 miRNA。使用 NTDs 小鼠模型和人类样本获得的测序数据来验证生物信息学结果。此外,使用双荧光素酶报告基因检测来验证鉴定的 miRNA-基因对之间的靶向关系。
共获得 104 个 NTDs 相关和神经外胚层肿瘤相关基因的交集基因;其中 20 个基因在 NTDs 样本中差异表达,且相互作用非常密切。在 10 个枢纽基因中,我们鉴定出 3 个在 RA 诱导的 NTDs 小鼠和人类脑胶质瘤样本中差异表达的重要易感基因:Ncam1、Shh 和 Ascl1。其中,我们发现 Ncam1 的表达水平受 mmu-miR-30a-5p 的调节,而 Ascl1 的表达水平受 mmu-miR-375-3p 的调节。
总之,我们鉴定了 NTDs 和神经外胚层肿瘤之间差异表达的基因和潜在的 miRNA 介导的调节机制,这可能为未来寻找 NTDs 或神经外胚层肿瘤的新治疗靶点的研究提供指导。