Central Role of C2H2-Type Zinc Finger-Containing Genes in Pediatric Brain Tumors

Dimitrios S. Kanakoglou, Andromachi Pampalou, Lina S. Malakou, E. Lakiotaki, T. Loupis, Dimitrios M. Vrachnos, Panayiotis D. Glekas, Alexia Klonou, A. Giannopoulou, Madison Carpenter, P. Korkolopoulou, C. Piperi
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Abstract

Zinc fingers consist of one of the most abundant motifs in transcription factors and DNA-binding proteins. Recent studies provide evidence on the pathological implication of zinc finger proteins in various neurodevelopmental disorders and malignancies but their role in pediatric brain tumors is largely unexplored. To this end, we investigated the differential expression of zinc finger-containing genes along with relevant biological processes and pathways among four main brain tumor categories (pilocytic astrocytomas, ependymomas, medulloblastomas and glioblastomas). By employing an extended bioinformatic toolset, we performed a preliminary in silico study in order to identify the expression of zinc finger-containing genes and associated functions in pediatric brain tumors. Our data analysis reveals the prominent role of C2H2-type zinc finger-containing genes in the molecular mechanisms underlying pediatric brain tumors followed by the Ring and PHD finger types. Significant dysregulation of ABLIM2 and UHFR1 genes was detected in all tumor types drawing attention to the dysregulation of cell polarization process and Ubiquitin-Proteasome System (UPS) in the pathogenesis of pediatric brain tumors. Moreover, significant gene clustering was observed in multiple locations with two highly visible clusters revealing a contrast in gene regulation between medulloblastomas and the other three brain tumor types, indicating a promising area of future research.
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C2H2型锌指基因在儿童脑肿瘤中的核心作用
锌指是转录因子和dna结合蛋白中最丰富的基序之一。最近的研究提供了锌指蛋白在各种神经发育障碍和恶性肿瘤中的病理意义的证据,但它们在儿童脑肿瘤中的作用在很大程度上未被探索。为此,我们研究了四种主要脑肿瘤(毛细胞星形细胞瘤、室管膜瘤、髓母细胞瘤和胶质母细胞瘤)中含锌指基因的差异表达及其相关的生物学过程和途径。通过使用扩展的生物信息学工具集,我们进行了初步的计算机研究,以确定含锌指基因的表达及其在儿童脑肿瘤中的相关功能。我们的数据分析揭示了c2h2型含锌指基因在儿童脑肿瘤分子机制中的突出作用,其次是Ring和PHD指型。ABLIM2和UHFR1基因在所有肿瘤类型中均存在显著的异常,引起人们对儿童脑肿瘤发病过程中细胞极化过程和泛素-蛋白酶体系统(Ubiquitin-Proteasome System, UPS)异常的关注。此外,在多个位置观察到显著的基因聚类,其中两个高度可见的聚类揭示了髓母细胞瘤与其他三种脑肿瘤类型之间基因调控的差异,这表明了未来研究的一个有前景的领域。
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