RRS1在神经母细胞瘤组织和细胞中的表达及意义

The expression and significance of RRS1 in neuroblastoma tissues and cells

目的探究核糖体合成调控因子1(RRS1)在神经母细胞瘤组织和细胞中的表达及意义。方法使用TARGET数据库分析RRS1在神经母细胞瘤组织中的表达情况,并分析RRS1高表达与神经母细胞瘤病理指标及预后之间的关联,随后使用GEO数据库分析RRS1在神经母细胞瘤细胞系中的表达情况。然后运用慢病毒转染技术过表达或敲低SK-N-AS细胞株中RRS1的表达,采用CCK-8法、平板克隆实验、流式细胞术和Transwell法检测RRS1对肿瘤细胞增殖、凋亡、周期分布和迁移的影响。结果TARGET和GEO数据库分析结果显示,RRS1基因在59例NB组织中高表达(59/150),且其在NB高风险组中的表达明显高于中、低风险组(P<0.01);此外,RRS1 mRNA在NB细胞系中的表达水平明显高于其在对照细胞中的表达(P<0.01)。临床病理相关性分析结果显示,RRS1mRNA的表达水平与NB患者的年龄、MYCN扩增、INSS分期、COG分期及NB患者的死亡(临床回访)(P<0.05)有关;Kaplan-Meier生存分析显示,RRS1高表达组NB患者的总生存时间(OS)较低表达患者的短(P<0.001)。细胞功能实验结果表明,RRS1过表达可促进SK-N-AS细胞株的增殖、周期进程和迁移并抑制细胞凋亡;而RRS1敲低时,实验显示相反的趋势。结论RRS1高表达可能与神经母细胞瘤患者的不良预后相关,其可参与调节神经母细胞瘤细胞的增殖、凋亡、周期进程和迁移。

Objective To investigate the expression and significance of Ribosome Biogenesis Regulator 1 Homolog(RRS1)in the tissues and cells of neuroblastoma.Methods TARGET database was used to analyze the expression of RRS1 in neuroblastoma tissues and the correlation between RRS1 expression and clinicopathological parameters and patient survival status.The GEO database was used to analyze the expression of RRS1 in neuroblastoma cell lines.Then,lentivirus transfection method was used to knockdown or overexpress RRS1 in SK-N-AS cells;CCK8 and Colony formation assay were used to detect cell proliferation,Flow cytometry(FCM)was used to detect cell apoptosis and cycle distribution,and Transwell assay was used to detect cell migration.Results Increased RRS1 level was found in 59 neuroblastoma cases(59/150).The expression of RRS1 gene in high-risk group was significantly higher than that in intermediate and low risk groups(P<0.01).In addition,compared with negative control cells,the expression of RRS1 gene was significantly increased in NB cell lines(P<0.05).The pathological analysis results showed,the expression level of RRS1 is associated with age,INSS stage,COG risk,MYCN amplification,and death(clinical follow-up)(P<0.05);Kaplan-meier survival analysis demonstrated that the high RRS1 expression group had shorter Overall survival(OS)compared with the low expression group(P<0.001).Cell function experiments indicated that RRS1 overexpression not only could promote cell proliferation,cycle progression and migration,but also inhibit cell apoptosis.Down-regulation of the expression of RRS1 showed the opposite result.Conclusions The high expression of RRS1 is associated with poor prognosis,and it may be involved in regulating cell proliferation,apoptosis,cycle progression and migration of neuroblastoma cell.