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m5C阅读器YBX1通过调节铁死亡抑制因子MS4A15的稳定性促进结直肠癌生长
The 5-methylcytosine reader Y-box binding protein 1 promotes the growth of colorectal cancer by regulating the stability of the ferroptosis inhibitor membrane-spanning 4-domains subfamily A 15
- 重庆医科大学学报 2025年50卷第11期 页码：1506-1514
- 作者机构：
1.成都医学院第一附属医院胃肠外科，成都 610500
2.川北医学院附属医院血管外科，南充 637000
3.川北医学院附属医院胃肠外科二，南充 637000
4.川北医学院第二临床医学院肛肠外科，南充 637000
- 作者简介：
夏术森，Email：xsx0639@163.com，研究方向：消化道肿瘤的基础与临床。
彭 洪，Email：1041910523@qq.com。
- 基金信息：四川省科技厅面上资助项目(2024NSFSC0737);四川省中医药管理局课题资助项目(2024MS590);四川省临床重点专科经费资助项目(ZX-2428-1);成都医学院第一附属医院科研启动基金(CYFY-GQ71);2024年医学影像四川省重点实验室开放课题(MIKL202407)
DOI：10.13406/j.cnki.cyxb.003738
中图分类号： R735.3收稿：2024-06-25，
修回：2024-08-29，
录用：2024-09-18，
纸质出版：2025-11-28
- 稿件说明：
移动端阅览
夏术森,朱彦斌,刘礼鑫等.m5C阅读器YBX1通过调节铁死亡抑制因子MS4A15的稳定性促进结直肠癌生长[J].重庆医科大学学报,2025,50(11):1506-1514.
Xia Shusen,Zhu Yanbin,Liu Lixin,et al.The 5-methylcytosine reader Y-box binding protein 1 promotes the growth of colorectal cancer by regulating the stability of the ferroptosis inhibitor membrane-spanning 4-domains subfamily A 15[J].Journal of Chongqing Medical University,2025,50(11):1506-1514.
夏术森,朱彦斌,刘礼鑫等.m5C阅读器YBX1通过调节铁死亡抑制因子MS4A15的稳定性促进结直肠癌生长[J].重庆医科大学学报,2025,50(11):1506-1514. DOI： 10.13406/j.cnki.cyxb.003738.
Xia Shusen,Zhu Yanbin,Liu Lixin,et al.The 5-methylcytosine reader Y-box binding protein 1 promotes the growth of colorectal cancer by regulating the stability of the ferroptosis inhibitor membrane-spanning 4-domains subfamily A 15[J].Journal of Chongqing Medical University,2025,50(11):1506-1514. DOI： 10.13406/j.cnki.cyxb.003738.
摘要
目的
2
探讨5-甲基胞嘧啶（5-methylcytosine，m5C）阅读器Y-框结合蛋白1 （Y-box binding protein1，YBX1）通过调节铁死亡抑制因子人跨膜结构域4亚家族成员15（Membrane-spanning 4-domains subfamily A 15，MS4A15）的稳定性参与结直肠癌发生发展的分子机制。
方法
2
通过生物信息学数据库分析YBX1 mRNA和蛋白在结肠癌中的表达。RT-qPCR法检测结直肠癌细胞中YBX1的表达水平。LC-MS法检测结直肠癌细胞和正常结直肠黏膜细胞中m5C修饰水平。CCK8法检测YBX1对结直肠癌细胞增殖的影响，Transwell法检测对结直肠癌细胞迁移能力的影响，流式细胞仪检测对结直肠癌细胞凋亡的影响。通过生物信息学方法分析可与YBX1相互作用的铁死亡抑制因子MS4A15和潜在m5C 修饰位点。通过GEPIA2分析YBX1表达与MS4A15的相关性。抑制YBX1表达并分析MS4A15 mRNA的表达水平及MS4A15的m5C修饰水平。通过catRAPID数据库寻找YBX1蛋白和MS4A15 mRNA的结合位点。抑制YBX1表达并用放线菌素D（actinomycinD）处理结直肠癌细胞，RT-qPCR法检测MS4A15 mRNA的稳定性。抑制MS4A15表达并检测细胞增殖活性，细胞迁移能力和细胞凋亡率，抑制MS4A15表达，检测铁死亡关键指标MDA、ROS和Fe
2+
的表达水平。
结果
2
YBX1 mRNA和蛋白在结直肠癌中高表达并且YBX1在结直肠癌细胞中高表达。结直肠癌细胞的m5C修饰水平明显高于正常结直肠黏膜细胞。YBX1可促进结直肠癌细胞增殖，迁移及抑制细胞凋亡。生物信息学分析证实YBX1与铁死亡抑制因子MS4A15表达水平呈正相关，并且MS4A15上存在多个潜在m5C修饰位点。抑制YBX1表达可降低MS4A15 mRNA表达水平及MS4A15基因的m5C修饰水平，并可降低MS4A15 mRNA的稳定性。抑制MS4A15表达后细胞增殖活性和细胞迁移能力明显降低，细胞凋亡率增高，MDA、ROS 和 Fe2+含量均明显增高。
结论
2
上述结果表明YBX1通过m5C修饰稳定MS4A15促进结直肠癌的发生和发展，为结直肠癌患者提供有前景的靶向治疗策略。
Abstract
Objective
2
To investigate the molecular mechanism of the 5-methylcytosine（m5C） reader Y-box binding protein 1（YBX1） in participating in the development and progression of colorectal cancer（CRC） by regulating the stability of the ferroptosis inhibitor membrane-spanning 4-domains subfamily A 15（MS4A15）.
Methods
2
Bioinformatics databases were used to investigate the mRNA and protein expression levels of YBX1 i
n CRC. RT-qPCR was used to measure the expression level of YBX1 in CRC cells. LC-MS was used to measure the level of m5C modification in CRC cells and normal colorectal mucosal cells. CCK-8 assay was used to observe the effect of YBX1 on the proliferation of CRC cells，Transwell assay was used to observe its effect on the migration ability of CRC cells，and flow cytometry was sued to observe its effect on the apoptosis of CRC cells. Bioinformatics methods were used to identify the ferroptosis inhibitors that can interact with YBX1 and potential m5C modification sites. GEPIA2 was used to analyze the association between the expression of YBX1 and MS4A15. The expression of YBX1 was inhibited，and then the mRNA expression level and m5C modification level of MS4A15 were analyzed. The catRAPID database was used to find the binding sites between YBX1 protein and MS4A15 mRNA. CRC cells were treated with actinomycin D after inhibition of YBX1 expression，and RT-qPCR was used to measure the stability of MS4A15 mRNA. The expression of MS4A15 was inhibited，and then the proliferative activity，migration ability，and apoptosis rate of cells were measured，as well as the expression levels of the key indicators for ferroptosis，including MDA，ROS，and Fe
2+
.
Results
2
High mRNA and protein expression levels of YBX1 were observed in CRC，and YBX1 was highly expressed in CRC cells. The m5C modification level of CRC cells was significantly higher than that of normal colorectal mucosal cells. YBX1 could promote the proliferation and migration of CRC cells and inhibit the apoptosis of CRC cells. The bioinformatics analysis showed that YBX1 was positively correlated with the expression level of the ferroptosis inhibitor MS4A15，and there were multiple m5C modification sites on MS4A15. Inhibition of YBX1 expression could reduce the mRNA expression level and m5C modification level of MS4A15 and the stability of MS4A15 mRNA. There were significant reductions in the proliferative activity and migration ability o
f CRC cells and a significant increase in the apoptosis rate of CRC cells after inhibition of MS4A15 expression，with significant increases in the content of MDA，ROS，and Fe
2+
.
Conclusion
2
These results show that YBX1 promotes the development and progression of CRC by stabilizing MS4A15 via m5C modification，which provides a promising targeted therapeutic strategy for CRC patients.
关键词
Keywords
references
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