Sevimoglu Tuba, Çalışkaner Zihni Onur
Department of Bioengineering, University of Health Sciences, Istanbul, Türkiye.
Department of Molecular Biology and Genetics, Biruni University, Istanbul, Türkiye.
Cell Biochem Biophys. 2025 Jun 26. doi: 10.1007/s12013-025-01808-0.
Cancer is one of the prominent causes of death, and brain cancer accounts for about 2% of this figure, with glioma being the major type. This study aims to identify biomarker candidates for glioma subtypes, specifically glioblastoma (GBM) and oligodendroglioma (ODG), as well as to disclose repurposed drug candidates common to these brain tumors. Gene expression profiles were analyzed and integrated with data from proteomics interactions as well as miRNA regulation. 23 mutual core DEGs (differentially expressed genes) were identified. Correlation networks and protein interaction networks were constructed from these core DEGs. Hubs of the protein interaction networks (CALM1), miRNA - core DEG interaction network (SOX4, MTHFD2, and CALM1), and correlation networks such as ABCA2, TPPP, PPP1R16B, SPOCK3, and SPARC, as well as central miRNAs (hsa-miR-1-3p, hsa-miR-19b-3p, and hsa-miR-335-5p) were identified. Furthermore, candidate therapeutic agents were revealed. Docking-based virtual screening suggests that budesonide, sirolimus, cephaeline, etoposide, and staurosporine may target proteins upregulated in GBM and ODG, such as APOC, MTHFD2, and LPL, in addition to their actual targets. Particularly, sirolimus and protriptyline exhibited comparable binding affinities against MTHFD2 (-11.23 kcal/mol) and LPL (-7.45 kcal/mol), respectively, compared to their actual targets. The holistic network-based approach applied in this study may be advantageous in the illumination of these subtypes and may aid in the design of improved therapeutics in treatment of the studied gliomas.
癌症是主要的死亡原因之一，脑癌约占这一数字的2%，其中胶质瘤是主要类型。本研究旨在确定胶质瘤亚型，特别是胶质母细胞瘤（GBM）和少突胶质细胞瘤（ODG）的生物标志物候选物，并揭示这些脑肿瘤共有的重新利用的药物候选物。分析了基因表达谱，并将其与蛋白质组学相互作用数据以及miRNA调控数据进行整合。确定了23个共同的核心差异表达基因（DEG）。从这些核心DEG构建了相关网络和蛋白质相互作用网络。确定了蛋白质相互作用网络的枢纽（CALM1）、miRNA-核心DEG相互作用网络（SOX4、MTHFD2和CALM1）以及相关网络，如ABCA2、TPPP、PPP1R16B、SPOCK3和SPARC，以及核心miRNA（hsa-miR-1-3p、hsa-miR-19b-3p和hsa-miR-335-5p）。此外，还揭示了候选治疗药物。基于对接的虚拟筛选表明，布地奈德、西罗莫司、千金藤碱、依托泊苷和星形孢菌素除了其实际靶点外，还可能靶向GBM和ODG中上调的蛋白质，如APOC、MTHFD2和LPL。特别是，与它们的实际靶点相比，西罗莫司和普罗替林分别对MTHFD2（-11.23 kcal/mol）和LPL（-7.45 kcal/mol）表现出相当的结合亲和力。本研究中应用的基于整体网络的方法可能有利于阐明这些亚型，并可能有助于设计出更好的治疗方法来治疗所研究的胶质瘤。
