Effect of the ribosome biogenesis factor BMS1 on proliferation of neuroblastoma cells
10.3969/j.issn.1006-7795.2025.02.016
- VernacularTitle:核糖体生物合成因子BMS1对神经母细胞瘤细胞增殖的影响
- Author:
Jinxin GUO
1
;
Anna JIA
1
;
Shijia ZHAN
1
;
Yao ZHANG
1
;
Xuan ZHANG
1
;
Yongli GUO
1
;
Yan CHANG
1
Author Information
1. 国家儿童医学中心 首都医科大学附属北京儿童医院 北京市儿科研究所 儿科重大疾病研究教育部重点实验室 儿童耳鼻咽喉头颈外科疾病北京市重点实验室,北京 100045
- Publication Type:Journal Article
- Keywords:
BMS1;
neuroblastoma;
cell proliferation;
p53;
MYCN
- From:
Journal of Capital Medical University
2025;46(2):296-305
- CountryChina
- Language:Chinese
-
Abstract:
Objective To elucidate the functional role and underlying mechanisms of the ribosome biogenesis factor BMS1 in neuroblastoma(NB)cellular proliferation.Methods We utilized the R2 genomics analysis and visualization platform to analyze the correlation between BMS1 expression levels and clinical characteristics of NB children.The BMS1 mRNA level in three human neuroblastoma cells SK-N-BE(2),BE(2)-C,IMR-32 and two normal cells hTERT RPE-1,IMR-90 was detected by real-time quantitative polymerase chain reaction(RT-qPCR).Two distinct small interfering RNA(siRNA)sequences were used to target BMS1 mRNA in NB cells SK-N-BE(2)and BE(2)-C,with normal cells hTERT RPE-1 serving as controls.We used RT-qPCR to quantify the mRNA levels of BMS1 and two key neuroblastoma-associated molecules(MYCN and p53).After transfection with siRNA,cellular proliferation was detected by various experimental approaches:crystal violet staining,real-time cell analysis(RTCA),colony-forming unit assay and immunofluorescence.Results By analyzing two independent neuroblastoma clinical cohorts(GSE85047/NRC-283 and Westermann-144 datasets),it was found that the BMS1 mRNA level in MYCN-amplified NB was significantly higher than that in MYCN-non-amplified NB(P<0.05).Furthermore,the overall survival rate of NB children in the BMS1 high-expression group was decreased(P<0.05).Consistent with these clinical observations,the BMS1 mRNA level in NB cells SK-N-BE(2),BE(2)-C and IMR-32 was significantly higher than that in normal cells hTERT RPE-1,IMR-90(P<0.05).The targeted transient knockdown of BMS1 in NB cell lines SK-N-BE(2)and BE(2)-C resulted in decreased intracellular MYCN mRNA expression levels(P<0.05),significantly reduced cell proliferation capacity and colony-forming ability(P<0.05).Immunofluorescence revealed that the expression of Ki-67,a proliferation marker,was decreased(P<0.05).At the molecular level,RT-qPCR showed that the p53 mRNA level was significantly elevated in the BMS1-knockdown groups(si BMS1-1#and si BMS1-2#)compared with the control group(P<0.05).However,transient knockdown of BMS1 had no significant impact on the proliferative capacity of normal cells hTERT RPE-1.Conclusion BMS1 expression was up-regulated in MYCN-amplified NB and negatively correlated with the prognosis of the NB children.Mechanistically,interfering with BMS1 expression may transcriptionally activate p53 in NB cells,thereby inhibiting their proliferative ability,while having minimal impact on normal cells growth kinetics.These findings suggest that BMS1 serves as an important proliferation driver in NB and is expected to be a promising therapeutic target for NB children,particularly MYCN-amplified pediatric patients.
