Amorós Morales Leslie C, Gómez Bergna Santiago M, Marchesini Abril, Scalise María Luján, Gonzalez Nazareno, Ferrelli M Leticia, Candolfi Marianela, Romanowski Víctor, Pidre Matias L
Instituto de Biotecnología y Biología Molecular (IBBM, UNLP-CONICET), Facultad de Ciencias Exactas, Universidad Nacional de La Plata, Consejo Nacional de Investigaciones Científicas y Técnicas, La Plata B1900, Argentina.
Instituto de Investigaciones Biomédicas (INBIOMED, UBA-CONICET), Facultad de Medicina, Universidad de Buenos Aires, Consejo Nacional de Investigaciones Científicas y Técnicas, Ciudad Autónoma de Buenos Aires C1121ABG, Argentina.
Int J Mol Sci. 2025 Jun 10;26(12):5555. doi: 10.3390/ijms26125555.
Diffuse gliomas (DGs) are malignant primary brain tumors originating from glial cells. This study aimed to investigate the role of Receptor-interacting protein kinase 1 (RIPK1) in DG pathology. The RIPK1 mRNA expression was analyzed in DG databases from The Cancer Genome Atlas (TCGA) containing clinical, genomic, and transcriptomic information from 670 patients. Transcriptomic studies were carried out using USC Xena and R, while in vitro assays were performed with the glioblastoma human cell line U251 and the commercial RIPK1 inhibitor GSK2982772. The results showed that high RIPK1 expression was linked to a lower survival probability in patients. Additionally, the RIPK1 expression was higher in the wtIDH samples compared to that in the mIDH samples. Significant differences in the expression of genes related to cellular dedifferentiation, proinflammatory cell death pathways, and tumor-infiltrating immune cells were found between high- and low-RIPK1 expression groups. To further characterize the role of RIPK1 in DG, the effects of the RIPK1 inhibitor were evaluated, alone or combined with cisplatin, on glioblastoma cell proliferation and apoptosis. The combined treatments effectively reduced cell proliferation and increased apoptosis. The overexpression of RIPK1 was associated with a poor prognosis for DG, suggesting that RIPK1 plays a critical role in glioma pathogenesis and should be considered in therapeutic decision-making.
弥漫性胶质瘤（DGs）是起源于神经胶质细胞的恶性原发性脑肿瘤。本研究旨在探讨受体相互作用蛋白激酶1（RIPK1）在DG病理学中的作用。在来自癌症基因组图谱（TCGA）的DG数据库中分析了RIPK1 mRNA表达，该数据库包含670例患者的临床、基因组和转录组信息。使用南加州大学Xena和R进行转录组研究，同时用胶质母细胞瘤人细胞系U251和商业RIPK1抑制剂GSK2982772进行体外试验。结果表明，RIPK1高表达与患者较低的生存概率相关。此外，wtIDH样本中的RIPK1表达高于mIDH样本。在RIPK1高表达组和低表达组之间，发现与细胞去分化、促炎细胞死亡途径和肿瘤浸润免疫细胞相关的基因表达存在显著差异。为了进一步表征RIPK1在DG中的作用，评估了RIPK1抑制剂单独或与顺铂联合对胶质母细胞瘤细胞增殖和凋亡的影响。联合治疗有效降低了细胞增殖并增加了凋亡。RIPK1的过表达与DG的不良预后相关，表明RIPK1在胶质瘤发病机制中起关键作用，在治疗决策中应予以考虑。
