Ren Pengwu, Yu Jiayan, Wang Dongxiang, Zeng Lijuan, Zhang Xianqiang, Liu Xiaohe, Cao Yongfu, Hu Zijian, Zhao Xiaoyong, Yang Kongbin
Department of Neurosurgery, Key Laboratory of Biological Targeting Diagnosis, Therapy and Rehabilitation of Guangdong Higher Education Institutes, Fifth Affiliated Hospital, Guangzhou Medical University, Guangzhou, Guangdong.
Department of Dermatology, The First Clinical Medical School of Guangzhou University of Chinese Medicine, Guangzhou, China.
Cytojournal. 2024 Oct 30;21:39. doi: 10.25259/Cytojournal_39_2024. eCollection 2024.
The literature has reported that Newcastle disease virus (NDV) can have inhibitory effects on various tumors. This study aims to investigate the mechanism by which NDV induces pyroptosis in medulloblastoma (MB) cells.
We treated MB cell lines Daoy and D283 with NDV or recombinant interferon-gamma (IFN-g) proteins. Guanylate-binding proteins (GBPs) were measured using real-time quantitative polymerase chain reaction. Small interfering RNA-specific targeting was transfected into MB cells. Apoptosis was assessed using Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nucleoside nick end labeling and flow cytometry assays. Pyroptosis-related proteins, including caspase-4, caspase-1, and gasdermin D (GSDMD), were detected using Western blotting.
Bioinformatics analysis revealed that GBP family genes and interferon-related genes might be responsive to NDV stimulation in MB cells. Treatment with NDV resulted in increased IFN-g levels and upregulated GBP expression, particularly . In addition, IFN-g treatment induced expression and enhanced cell apoptosis. knockdown attenuated the decreased cell proliferation and increased cell apoptosis induced by NDV in MB cells. overexpression upregulated the expression of pyroptosis-related proteins, including caspase-4, caspase-1, and GSDMD, subsequently leading to inhibition of cell proliferation and an increase in cell apoptosis levels. The silencing of caspase-4 confirmed the regulatory role of in MB cell pyroptosis.
Our findings suggest that NDV elevates IFN-g and expression in MB cells, potentially contributing to caspase-4-mediated pyroptosis activation.
文献报道新城疫病毒（NDV）对多种肿瘤具有抑制作用。本研究旨在探讨NDV诱导髓母细胞瘤（MB）细胞焦亡的机制。
我们用NDV或重组干扰素-γ（IFN-γ）蛋白处理MB细胞系Daoy和D283。使用实时定量聚合酶链反应测量鸟苷酸结合蛋白（GBPs）。将特异性靶向的小干扰RNA转染到MB细胞中。使用末端脱氧核苷酸转移酶介导的脱氧尿苷三磷酸核苷缺口末端标记和流式细胞术检测细胞凋亡。使用蛋白质免疫印迹法检测焦亡相关蛋白，包括半胱天冬酶-4、半胱天冬酶-1和gasdermin D（GSDMD）。
生物信息学分析表明，GBP家族基因和干扰素相关基因可能对MB细胞中的NDV刺激有反应。用NDV处理导致IFN-γ水平升高和GBP表达上调，尤其是[具体内容缺失]。此外，IFN-γ处理诱导[具体内容缺失]表达并增强细胞凋亡。[具体内容缺失]敲低减弱了NDV诱导的MB细胞增殖减少和细胞凋亡增加。[具体内容缺失]过表达上调了焦亡相关蛋白的表达，包括半胱天冬酶-4、半胱天冬酶-1和GSDMD，随后导致细胞增殖受到抑制，细胞凋亡水平增加。半胱天冬酶-4的沉默证实了[具体内容缺失]在MB细胞焦亡中的调节作用。
我们的研究结果表明，NDV提高了MB细胞中IFN-γ和[具体内容缺失]的表达，可能有助于半胱天冬酶-4介导的焦亡激活。
