南方医科大学学报

南方医科大学学报 ›› 2025, Vol. 45 ›› Issue (10): 2240-2249.doi: 10.12122/j.issn.1673-4254.2025.10.20

• • 上一篇    

高表达SF3B3促进胃癌细胞恶性增殖并与患者不良预后相关

鲁辉1,2(), 宋博文1,2, 施金冉3, 王舜印3, 陈孝华1,2, 杨晶晶1,2, 葛思堂1,4, 左芦根1,4()   

  1. 1.蚌埠医科大学第一附属医院，胃肠外科，安徽 蚌埠 233004
    4.蚌埠医科大学第一附属医院，炎症相关性疾病基础与转化研究安徽省重点实验室，安徽 蚌埠 233004
    2.蚌埠医科大学研究生院，安徽 蚌埠 233030
    3.蚌埠医科大学，安徽 蚌埠 233030
  • 收稿日期:2025-02-16 出版日期:2025-10-20 发布日期:2025-10-24
  • 通讯作者: 左芦根 E-mail:Lu15855787559@163.com;zuolugen@126.com
  • 作者简介:鲁 辉，在读硕士研究生，E-mail: Lu15855787559@163.com
  • 基金资助:
    安徽省卫生健康科研项目(AHWJ2022a019);蚌埠医科大学研究生科研创新计划项目(Byycxz24020);大学生创新创业训练计划项目(202410367039)

SF3B3 overexpression promotes proliferation of gastric cancer cells and correlates with poor patient prognosis

Hui LU1,2(), Bowen SONG1,2, Jinran SHI3, Shunyin WANG3, Xiaohua CHEN1,2, Jingjing YANG1,2, Sitang GE1,4, Lugen ZUO1,4()   

  1. 1.Department of Gastrointestinal Surgery, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China
    4.Anhui Provincial Key Laboratory of Basic and Translational Research of Inflammation-related Diseases, First Affiliated Hospital of Bengbu Medical University, Bengbu 233004, China
    2.Graduate School, Bengbu Medical University, Bengbu 233030, China
    3.Bengbu Medical University, Bengbu 233030, China
  • Received:2025-02-16 Online:2025-10-20 Published:2025-10-24
  • Contact: Lugen ZUO E-mail:Lu15855787559@163.com;zuolugen@126.com

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摘要：

目的 分析SF3B3在胃癌发展和预后中的作用，并探讨其潜在机制。 方法 利用TIMER2.0、GEPIA和UALCAN数据库分析SF3B3在多种癌症和胃癌中的表达模式，并通过胃癌组织免疫组化验证。通过Kaplan-Meier Plotter数据库及本院队列构建K-M生存曲线，采用Cox回归筛选术后5年生存的独立危险因素，通过ROC曲线AUC值评估预测价值。生物信息学富集分析预测SF3B3在胃癌中可能参与的生物学过程。通过慢病毒介导的SF3B3干扰和过表达，结合CCK-8及Transwell迁移和侵袭方法，探究SF3B3对胃癌细胞增殖、迁移和侵袭能力的影响。免疫印迹法检测SF3B3对糖酵解关键蛋白表达的影响，通过测定细胞外酸化率（ECAR）探究SF3B3对糖酵解活性的作用。通过裸鼠成瘤实验，观察SF3B3对瘤体大小及对糖酵解关键蛋白表达的影响。 结果 SF3B3在胃癌中高表达，且与患者较差的预后相关（P<0.05）。多变量Cox回归分析显示，影响胃癌患者术后5年生存率的独立危险因素是高表达SF3B3、CEA≥5 μg/L、CA19-9≥37 kU/L、肿瘤分期的T3-4期以及淋巴结转移分期的N2-3期（P<0.05）。生物信息学分析显示糖酵解显著富集。干扰SF3B3削弱了HGC-27细胞的增殖、迁移和侵袭能力，而过表达SF3B3相反（P<0.05）。免疫印迹分析显示，SF3B3干扰降低HK2、PKM2、LDHA蛋白的表达，而过表达则相反（P<0.05）。ECAR实验显示，敲低SF3B3降低HGC-27细胞的ECAR，而过表达呈升高趋势（P<0.05）。裸鼠成瘤实验结果显示，与对照组相比，SF3B3干扰组肿瘤质量减少，HK2、PKM2、LDHA蛋白表达下调，而SF3B3过表达组显示出相反趋势（P<0.05）。 结论 SF3B3过表达与胃癌患者的不良预后密切相关，其可能通过增强糖酵解作用促进胃癌细胞的增殖、迁移和侵袭能力。

关键词: 胃癌, SF3B3, 不良预后, 糖酵解

Abstract:

Objective To investigate the role of SF3B3 in gastric cancer (GC) progression and prognosis and its possible mechanisms. Methods SF3B3 expression levels in pan-cancer and GC were analyzed using TIMER2.0, GEPIA, and UALCAN databases and validated using immunohistochemistry in GC tissues. Survival curves of GC patients were established using Kaplan-Meier Plotter and the data of a patient cohort our hospital. The independent risk factors for 5-year postoperative survival were identified using Cox regression, and their predictive values were evaluated using ROC analysis. SF3B3-associated biological processes were predicted by bioinformatics enrichment analyses. In GC HGC-27 cells, the effects of lentivirus-mediated SF3B3 knockdown and overexpression on cell proliferation and migration were investigated, and the changes in the key glycolytic proteins and extracellular acidification rate (ECAR) were detected. The influence of SF3B3 expression level on tumorigenesis and glycolytic protein expression in vivo were evaluated in a nude mouse xenograft model. Results High expression of SF3B3 in GC was associated with poor patient prognosis (P<0.05). The factors affecting 5-year survival outcomes following gastric oncological resection included high SF3B3 expression, a CEA level ≥5μg/L, a CA19-9 level ≥37 kU/L, tumor stage T3-4, and lymph node metastasis stage N2-3 (P<0.05). Bioinformatics analysis showed significant enrichment of SF3B3 in glycolysis. In HGC-27 cells, SF3B3 knockdown significantly inhibited while SF3B3 overexpression enhanced cell proliferation, migration, and invasion. SF3B3 knockdown obviously decreased the expressions of HK2, PKM2 and LDHA proteins and ECAR in HGC-27 cells, whereas SF3B3 overexpression produced the opposite effect. In nude mouse xenograft models, SF3B3 knockdown significantly reduced tumor mass and downregulated expression of HK2, PKM2 and LDHA proteins, and SF3B3 overexpression induced the opposite changes. Conclusion SF3B3 overexpression is associated with poor prognosis of GC patients and promotes GC cell proliferation, migration and invasion possibly by enhancing glycolysis.

Key words: gastric cancer, SF3B3, poor prognosis, glycolysis