中心体蛋白89促进神经母细胞瘤细胞系体外增殖

doi:10.16352/j.issn.1001-6325.2026.06.0836

基础医学与临床 ›› 2026, Vol. 46 ›› Issue (6): 836-844.doi: 10.16352/j.issn.1001-6325.2026.06.0836

中心体蛋白89促进神经母细胞瘤细胞系体外增殖

管晓星¹, 郭金鑫², 张朦¹, 贾超¹, 常艳², 张璇², 何乐建^1*

1.国家儿童医学中心首都医科大学附属北京儿童医院病理科,北京 100045;
2.国家儿童医学中心首都医科大学附属北京儿童医院儿科重大疾病研究教育部重点实验室北京市儿科研究所儿童耳鼻咽喉头颈外科疾病北京市重点实验室,北京 100045

收稿日期:2025-06-06 修回日期:2025-09-24 出版日期:2026-06-05 发布日期:2026-05-27
通讯作者: ^*lejianhe@sina.com
基金资助:
北京研究型病房卓越计划(BRWEP2024W102090104);北京市自然科学基金(7252046,7244341);首都医科大学附属北京儿童医院儿医青年人人创项目(QNRRC-202401)

Centrosomal protein 89 promotes the proliferation of neuroblastoma cell lines in vitro

GUAN Xiaoxing¹, GUO Jinxin², ZHANG Meng¹, JIA Chao¹, CHANG Yan², ZHANG Xuan², HE Lejian^1*

1. Department of Pathology;
2. Beijing Key Laboratory for Pediatric Diseases of Otolaryngology,Head and Neck Surgery, MOE Key Laboratory of Major Diseases in Children,Beijing Pediatric Research Institute,Beijing Children′s Hospital, Capital Medical University,National Center for Children′s Health,Beijing 100045,China

Received:2025-06-06 Revised:2025-09-24 Online:2026-06-05 Published:2026-05-27
Contact: ^*lejianhe@sina.com

摘要/Abstract

摘要： 目的探究中心体蛋白89(CEP89)在神经母细胞瘤(NB)中的功能。方法利用R2数据库分析NB临床样本中CEP89表达水平与患儿预后的关系;免疫组化检测NB临床样本和癌旁组织中CEP89表达;RT-qPCR检测NB细胞系BE(2)-M17、SK-N-BE(2)、SH-SY5Y和正常细胞系MCF10A、IMR-90、hTERT RPE-1中CEP89 mRNA表达量;利用siRNA构建瞬时敲低CEP89的细胞,shRNA慢病毒感染构建稳定敲低CEP89的细胞;结晶紫染色和实时无标记细胞分析(RTCA)检测细胞增殖;集落形成实验检测细胞集落形成能力;流式细胞术检测NB细胞凋亡和细胞周期比例;细胞划痕实验检测细胞迁移;免疫荧光及Western blot检测Ki67蛋白表达。结果 R2数据库分析发现CEP89高表达组患儿生存率显著低于低表达组。与癌旁组织相比,NB肿瘤中CEP89的蛋白水平显著升高;NB细胞系中CEP89的mRNA表达量显著高于正常细胞系。结晶紫染色、RTCA和集落形成实验结果显示,敲低CEP89显著抑制了NB细胞增殖,但对正常细胞的影响不显著;干扰CEP89表达后NB细胞迁移率显著降低,在NB细胞中敲低CEP89后细胞凋亡水平增强,增殖标志分子Ki67蛋白表达降低。结论 CEP89在NB临床样本及NB细胞系中高表达。CEP89促进神经母细胞瘤细胞系体外增殖。

关键词: 神经母细胞瘤, 中心体蛋白89 (CEP89), 增殖, 迁移, 凋亡

Abstract: Objective To explore the function of centrosomal protein 89 (CEP89) in neuroblastoma (NB). Methods The relationship between the expression of CEP89 mRNA and the prognosis of NB patients was clarified through the analysis of three independent primary NB cohorts via Genomics Analysis and Visualization Platform R2. CEP89 protein was examined by immunohistochemical staining in tumors and adjacent tissues from NB patients. CEP89 mRNA in NB cell lines BE(2)-M17,SK-N-BE(2),SH-SY5Y and normal cell lines MCF10A,IMR-90 and hTERT RPE-1 was analyzed by RT-qPCR. Cell lines were transfected with CEP89-targeting siRNA or shRNA. Cell proliferation was detected by crystal violet staining,real time cell analysis (RTCA) and colony formation assays. Cell apoptosis and cell cycle were detected by flow cytometry and cell-cycle analysis. Wound-healing assay was performed to measure cell migration in vitro. Ki67 was analyzed by Western blot and immunofluorescence assay. Results Analysis of R2 database revealed that higher CEP89 expression was associated with poorer survival in NB patients. CEP89 protein expression level was significantly higher in NB patients tumors compared with adjacent tissues. CEP89 showed significantly increased expression at mRNA level in NB cells compared with non-NB normal cells. CEP89 knockdown reduced NB cell viability more significantly compared with normal cells as demonstrated by crystal violet staining,RTCA and colony formation assays. CEP89 knockdown significantly induced apoptosis,limited cell migration,and decreased the expression of Ki67 in NB cells. Conclusions CEP89 expression is significantly increased in NB tumors and NB cells. CEP89 promotes the NB cell proliferation in vitro.

Key words: neuroblastoma, centrosomal protein 89(CEP89), proliferation, migration, apoptosis

中图分类号:

R739.43

管晓星, 郭金鑫, 张朦, 贾超, 常艳, 张璇, 何乐建. 中心体蛋白89促进神经母细胞瘤细胞系体外增殖[J]. 基础医学与临床, 2026, 46(6): 836-844.

GUAN Xiaoxing. Centrosomal protein 89 promotes the proliferation of neuroblastoma cell lines in vitro[J]. Basic & Clinical Medicine, 2026, 46(6): 836-844.

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中心体蛋白89促进神经母细胞瘤细胞系体外增殖

Centrosomal protein 89 promotes the proliferation of neuroblastoma cell lines in vitro

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