Vartholomatos Evrysthenis, Mantziou Stefania, Alexiou George A, Lazari Diamanto, Sioka Chrissa, Kyritsis Athanassios, Markopoulos Georgios S
Neurosurgical Institute, Faculty of Medicine, School of Health Sciences, University of Ioannina, 451 10 Ioannina, Greece.
Haematology Laboratory, Unit of Molecular Biology, University Hospital of Ioannina, 455 00 Ioannina, Greece.
Biomedicines. 2022 Apr 19;10(5):935. doi: 10.3390/biomedicines10050935.
High-grade gliomas are among the most aggressive malignancies, with significantly low median survival. Recent experimental research in the field has highlighted the importance of natural substances as possible antiglioma agents, also known for their antioxidant and anti-inflammatory action. We have previously shown that natural substances target several surface cluster of differentiation (CD) markers in glioma cells, as part of their mechanism of action. We analyzed the genome-wide NF-κB binding sites residing in consensus regulatory elements, based on ENCODE data. We found that NF-κB binding sites reside adjacent to the promoter regions of genes encoding CD markers targeted by antiglioma agents (namely, CD15/FUT4, CD28, CD44, CD58, CD61/SELL, CD71/TFRC, and CD122/IL2RB). Network and pathway analysis revealed that the markers are associated with a core network of genes that, altogether, participate in processes that associate tumorigenesis with inflammation and immune evasion. Our results reveal a core regulatory network that can be targeted in glioblastoma, with apparent implications in individuals that suffer from this devastating malignancy.
高级别胶质瘤是最具侵袭性的恶性肿瘤之一，中位生存期显著较低。该领域最近的实验研究强调了天然物质作为可能的抗胶质瘤药物的重要性，这些物质还以其抗氧化和抗炎作用而闻名。我们之前已经表明，天然物质靶向胶质瘤细胞中的几种表面分化簇（CD）标志物，这是它们作用机制的一部分。我们基于ENCODE数据，分析了存在于共有调控元件中的全基因组NF-κB结合位点。我们发现NF-κB结合位点位于编码抗胶质瘤药物靶向的CD标志物的基因（即CD15/FUT4、CD28、CD44、CD58、CD61/SELL、CD71/TFRC和CD122/IL2RB）的启动子区域附近。网络和通路分析表明，这些标志物与一个基因核心网络相关，这些基因共同参与将肿瘤发生与炎症和免疫逃逸联系起来的过程。我们的结果揭示了一个可在胶质母细胞瘤中靶向的核心调控网络，这对患有这种毁灭性恶性肿瘤的个体具有明显的意义。
