酪氨酸3单加氧酶/色氨酸5单加氧酶激活蛋白ζ在乳腺癌组织中的表达水平及其对乳腺癌细胞生物学功能的影响  

Expression of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta in breast cancer tissues and its effect on the biological function of breast cancer cells

作　　者：谷静[1] 闫雷 黄剑 GU Jing;YAN Lei;HUANG Jian(Department of Medical Laboratory,Huai′an First Hospital Affiliated to Nanjing Medical University,Huaian 223300,Jiangsu,China)

机构地区：[1]南京医科大学附属淮安第一医院检验科,江苏淮安223300

出　　处：《临床检验杂志》2025年第3期227-232,共6页Chinese Journal of Clinical Laboratory Science

基　　金：南京医科大学科技发展项目(NMUB20210133)。

摘　　要：目的 探讨酪氨酸3单加氧酶/色氨酸5单加氧酶激活蛋白ζ(YWHAZ)在乳腺癌组织中的表达水平及其对乳腺癌细胞系MCF-7细胞增殖、迁移以及侵袭能力的影响。方法 采用实时荧光定量PCR(qRT-PCR)检测96例乳腺癌患者癌组织中YWHAZ基因的表达水平;采用Pearson法分析癌组织中YWHAZ的表达水平与患者临床病理参数及预后的关系;通过CCK-8法、[JP2]细胞划痕试验、Transwell试验验证下调YWHAZ对MCF-7细胞增殖、迁移和侵袭能力的影响,采用Western blot检测上皮-间[JP]质转化(EMT)相关蛋白E-cadherin和Vimentin表达水平的变化。结果 三阴性乳腺癌(2.659±0.214,t=2.815,P=0.012)和非三阴性乳腺癌(1.822±0.165,t=5.079,P=0.001)患者癌组织中YWHAZ的表达水平较癌旁组织均显著上调;乳腺癌组织中YWHAZ的表达水平与血管浸润、淋巴结转移、远处转移、TNM分期、病理分型以及复发情况有关(P<0.05);在乳腺癌TNM[JP1]Ⅰ[JP]~[JP1]Ⅳ[JP]期患者中,高水平YWHAZ患者的无复发生存率(χ^(2)=31.10,P<0.0001)和总体生存率(χ^(2)=18.99,P<0.0001)较低水平YWHAZ患者均显著缩短;YWHAZ水平是乳腺癌患者预后较差的独立危险因素;下调YWHAZ能够抑制MCF-7细胞增殖(F=10.73,P=0.0004)、迁移(t=20.88,P=0.0023)和侵袭(t=13.72,P=0.0002)能力;Western blot证实下调YWHAZ表达后,E-cadherin蛋白水平升高(4.478±0.832,t=8.45,P=0.0137),但Vimentin蛋白水平下调(0.549±0.143,t=6.86,P=0.0206)。结论 YWHAZ异常高表达与乳腺癌发生、发展以及不良预后密切相关,下调YWHAZ能够抑制乳腺癌细胞系MCF-7增殖、迁移、侵袭以及EMT进展。Objective To investigate the expression level of tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta(YWHAZ)in breast cancer tissues and its effect on the proliferation,migration,and invasion ability of breast cancer MCF-7 cells.Methods Real-time quantitative PCR(qRT-PCR)was used to detect the expression levels of YWHAZ in the cancer tissues of 96 breast cancer patients.The correlations of the expression levels of YWHAZ in cancer tissues with clinical pathological parameters and prognosis of the patients were analyzed by the Pearson method.The effects of down-regulating YWHAZ on the proliferation,migration,and invasion ability of MCF-7 cells were verified by the CCK-8,cell scratch,and Transwell assays.The changes in the expression levels of epithelial-mesenchymal transition(EMT)related proteins such as E-cadherin and Vimentin were detected by the Western blot.Results The expression levels of YWHAZ in cancer tissues of patients with triple-negative breast cancer(2.659±0.214,t=2.815,P=0.012)and non-triple-negative breast cancer(1.822±0.165,t=5.079,P=0.001)were significantly higher than that in adjacent tissues.The expression levels of YWHAZ in breast cancer tissues were related to vascular invasion,lymph node metastasis,distant metastasis,TNM stage,pathological classification and recurrence(P<0.05).Among the breast cancer patients with TNM stages I to[JP1]Ⅳ[JP],the recurrence-free survival rate(χ^(2)=31.10,P<0.0001)and overall survival rate(χ^(2)=18.99,P<0.0001)of patients with higher levels of YWHAZ were significantly shorter than those of patients with lower levels of YWHAZ.The expression level of YWHAZ was an independent risk factor for the poor prognosis of breast cancer patients.The down-regulation of YWHAZ could inhibit the proliferation(F=10.73,P=0.0004),migration(t=20.88,P=0.0023)and invasion(t=13.72,P=0.0002)ability of MCF-7 cells.Western blot confirmed that down-regulating the expression of YWHAZ could lead to an increase in the levels of E-cadherin protein(4.478±0.832,t=8.45

关 键 词：乳腺癌 酪氨酸3单加氧酶/色氨酸5单加氧酶激活蛋白ζ 迁移 侵袭 上皮-间质转化 

分 类 号：R446.8[医药卫生—诊断学]