Analysis of Genes Associated with Both Neural Tube Defects and Neuroectodermal Tumors

神经管缺陷和神经外胚层肿瘤相关基因分析

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作者:Rui Cao, Jiaqi Li, Li Zhang, Jianting Li, Yuxiang Liang, Ruifang Ao, Ying Wang, Hang Li, Xin Lu, Zhizhen Liu, Hong Zhao, Jun Xie

Abstract

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.

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