TOMM40L促进三阴性乳腺癌细胞增殖和迁移并与不良预后相关  

TOMM40L promotes proliferation and migration of triple negative breast cancer cells and correlates with poor prognosis

作　　者：张柯 陆江宁 孙立新 遇珑 孙力超 冉宇靓 ZHANG Ke;LU Jiangning;SUN Lixin;YU Long;SUN Lichao;RAN Yuliang(State Key Laboratory of Molecular Oncology,National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital,CAMS&PUMC,Beijing 100021,China)

机构地区：[1]国家癌症中心/国家肿瘤临床医学研究中心/中国医学科学院,北京协和医学院,肿瘤医院分子肿瘤学国家重点实验室,北京100021

出　　处：《基础医学与临床》2025年第5期575-582,共8页Basic and Clinical Medicine

基　　金：国家自然科学基金(82373078)。

摘　　要：目的探讨TOMM40L在三阴性乳腺癌(TNBC)的表达情况与临床特征的相关性。方法利用UALCAN和TCGA数据库中的转录组数据评估TOMM40L在TNBC组织中的表达差异。采用单因素及多因素Cox回归分析并建立Nomogram模型评价TOMM40L在TNBC患者中的预后价值。通过蛋白质印迹法和实时荧光定量聚合酶链式反应(qPCR)验证TOMM40L在TNBC细胞系中的差异表达。利用特异性小分子干扰RNA(siRNA)敲降TOMM40L以分析其在TNBC细胞增殖和迁移中的作用。通过GO、KEGG及GSEA分析TOMM40L在TNBC中的潜在信号通路。结果与非TNBC肿瘤组织相比,TOMM40L在TNBC组织中高表达(P<0.001)。蛋白质印迹法和qPCR结果显示,TNBC细胞系中mRNA及蛋白质表达水平显著高于非TNBC细胞系(P<0.001)。CCK-8法和Transwell小室法实验结果表明,TOMM40L敲降后TNBC细胞系(LTT和MDA-MB-468)中的增殖、迁移能力显著降低。功能富集分析结果表明TOMM40L参与糖代谢相关途径。结论TOMM40L在TNBC细胞系和组织中高表达且与不良预后相关,此外,敲降TOMM40L可显著抑制TNBC细胞系的增殖和迁移。Objective To explore the clinical significance and to investigate the expression of TOMM40L in the tissue of triple-negative breast cancer(TNBC).Methods The expression of TOMM40L in TNBC tissues and normal tissues was analyzed with TCGA and UALCAN databases.Univariate and multivariate Cox regression analysis and Nomogram model were used to evaluate the prognostic value of TOMM40L in TNBC patients.Furthermore,the expression of TOMM40L in breast cancer cell lines was evaluated using Western blot analysis and quantitative real-time PCR.Specific siRNA knockdown was performed to evaluate the migration,and cell proliferation of TOMM40L.The potential signaling pathways of TOMM40L were identified by GO and KEGG and GSEA.Results TOMM40L was highly expressed in the TNBC compared to non-TNBC tumor tissues(P<0.001).TOMM40L levels were enhanced in TNBC cell lines as compared to other non-TNBC cell lines.CCK-8 and Transwell assay demonstrated that TOMM40L knockdown reduced the proliferation and migration of TNBCcell lines.Functional enrichment analysis showed that TOMM40L was involved in glucose metabolism-related pathways.Conclusions The expression of TOMM40L is increased in TNBC and is correlated with poor prognosis.TOMM40L may promote TNBC migration and proliferation.

关 键 词：三阴性乳腺癌 TOMM40L 临床意义 

分 类 号：R737.9[医药卫生—肿瘤]