Medical Oncology Department, Pediatric Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing Key Laboratory of Pediatric Hematology Oncology, National Key Clinical Discipline of Pediatric Oncology, Key Laboratory of Major Diseases in Children, Ministry of Education, Beijing 100045, China.
Laboratory of Tumor Immunology Beijing Pediatric Research Institute Beijing Children's Hospital Capital Medical University National Center for Children's Health, Beijing 100045, China.
Acta Biochim Biophys Sin (Shanghai). 2023 Mar 25;55(3):356-366. doi: 10.3724/abbs.2023020.
Neuroblastoma (NB) is a pediatric cancer of the peripheral sympathetic nervous system and represents the most frequent solid malignancy in infants. Nectin2 belongs to the immunoglobulin superfamily and has been shown to play a role in tumorigenesis. In the current study, we demonstrate that serum Nectin2 level is increased in NB patients compared with that in healthy controls and Nectin2 level is correlated with neuroblastoma international neuroblastoma staging system (INSS) classification. There is a positive correlation between Nectin2 level and shorter overall survival in NB patients. Knockdown of reduces the migration of SH-SY5Y and SK-N-BE2 cells and induces their apoptosis and cell cycle arrest. RNA-seq analysis demonstrates that knockdown affects the expressions of 258 genes, including 240 that are upregulated and 18 that are downregulated compared with negative controls. qRT-PCR and western blot analysis confirm that ANXA2 expression is decreased in -knockdown SH-SY5Y cells, consistent with the RNA-seq results. ANXA2 overexpression rescues the percentage of apoptotic NB cells induced by knockdown and compensates for the impact of knockdown on cleaved caspase3 and bax expressions. In addition, western blot analysis results show that ANXA2 overexpression rescues the effect of knockdown on MMP2 and MMP9 expressions. The current data highlight the importance of Nectin2 in NB progression and the potential of Nectin2 as a novel candidate target for gene therapy.
神经母细胞瘤（NB）是一种起源于外周交感神经系统的儿童期癌症，是婴儿最常见的实体恶性肿瘤。 nectin2 属于免疫球蛋白超家族，已被证明在肿瘤发生中起作用。在本研究中，我们证明 NB 患者的血清 nectin2 水平高于健康对照组，并且 nectin2 水平与神经母细胞瘤国际神经母细胞瘤分期系统（INSS）分类相关。在 NB 患者中，nectin2 水平与总生存期缩短呈正相关。下调 减少了 SH-SY5Y 和 SK-N-BE2 细胞的迁移，并诱导其凋亡和细胞周期停滞。 RNA-seq 分析表明，下调 影响了 258 个基因的表达，包括与阴性对照相比上调的 240 个基因和下调的 18 个基因。 qRT-PCR 和 Western blot 分析证实，与 RNA-seq 结果一致，下调 SH-SY5Y 细胞中的 ANXA2 表达。 ANXA2 的过表达挽救了由 下调诱导的 NB 细胞凋亡的百分比，并补偿了 下调对 cleaved caspase3 和 bax 表达的影响。此外，Western blot 分析结果表明，ANXA2 的过表达挽救了下调对 MMP2 和 MMP9 表达的影响。这些数据强调了 nectin2 在 NB 进展中的重要性，以及 nectin2 作为基因治疗新候选靶点的潜力。
