摘要
目的探讨泛素蛋白连接酶E3A(ubiquitin protein ligase E3A,UBE3A)与泛素特异性蛋白酶25(ubiquitin specific protease 25,USP25)在乳腺癌组织中的表达及与临床病理特征的相关性,并分析UBE3A与USP25在乳腺癌泛素蛋白酶体系统中的关系。方法采用免疫组织化学染色检测50例乳腺癌组织及癌旁相对正常组织石蜡标本中UBE3A与USP25的表达情况,并分析它们与乳腺癌患者临床病理特征的关系;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞,通过荧光定量PCR与Western Blot检测UBE3A基因及蛋白的敲减水平,然后观察敲减UBE3A后USP25的表达水平。结果UBE3A与USP25在乳腺癌组织中的阳性表达率分别为64%、72%,而在邻近相对正常组织中的表达均为阴性,两者在乳腺癌组织与相对正常组织中的表达差异具有统计学意义(P<0.001);UBE3A的表达与淋巴结转移(P=0.001)、Ki-67的表达(P<0.001)相关,USP25的表达与组织学分级(P=0.046)、淋巴结转移(P=0.041)、Ki-67的表达(P=0.029)相关;shRNA-UBE3A慢病毒转染乳腺癌MCF-7细胞后,UBE3A蛋白及mRNA的表达均明显降低(P<0.001),且敲减UBE3A后USP25的蛋白及mRNA的表达明显降低(P<0.001)。结论UBE3A与USP25和乳腺癌细胞的增殖、转移等生物学行为相关,在乳腺癌泛素蛋白酶体系统中UBE3A与USP25功能作用明显增强且保持动态平衡,它们可能共同作用促进乳腺癌的的发生发展。
Objective To investigate the expression of UBE3A and USP25 in breast cancer and its relationship with clinicopathological features,and to analyze the relationship between UBE3A and USP25 in the ubiquitin proteasome system of breast cancer.Methods UBE3A and USP25 protein expression was investigated by EnV ision immunohistochemical staining in 50 paraffin-embedded breast cancer tissue specimens and adjacent normal tissues,and the relation between them and clinicopathological characteristics was statistically analyzed.After shRNA-UBE3A lentivirus was transfected into breast cancer MCF-7 cells,and UBE3A gene was detected by fluorescence quantitative PCR and Western Blot,then the expression of USP25 was observed after UBE3A was knocked down.Results The positive expression rates of UBE3A and USP25 were 64%and 72%in breast cancer tissues,while they were negatively expressed in the adjacent normal tissues,and the differences were statistically significant(P<0.001);The expression level of UBE3A was associated with lymph node metastasis(P=0.001)and Ki-67 expression(P<0.001),the expression level of USP25 was associated with histological grade(P=0.046),lymph node metastasis(P=0.041)and Ki-67 expression(P=0.029).After shRNA-UBE3A lentivirus was transfected into breast cancer MCF-7 cells,the expression of UBE3A protein and gene was significantly decreased(P<0.001),and after UBE3A was knock-downed,protein and mRNA of USP25 were significantly down-expressed(P<0.001).Conclusion UBE3A and USP25 could be tightly associated with proliferation and metastasis,the functions of UBE3A and USP25 are significantly enhanced and keep a dynamic balance in the ubiquitin proteasome system of breast cancer,which may work together to promote the occurrence and development of breast cancer.
作者
荣欣欣
黄红梅
李静佳
侯令密
刘家有
李金穗
谢少利
杨懿
邓世山
RONG Xinxin;HUANG Hongmei;LI Jingjia;HOU Lingmi;LIU Jiayou;LI Jinsui;XIE Shaoli;YANG Yi;DENG Shishan(Department of Anatomy,North Sichuan Medical College,Nanchong 637000,China;不详)
出处
《实用医学杂志》
CAS
北大核心
2020年第1期27-32,共6页
The Journal of Practical Medicine
基金
四川省教育厅科研创新团队项目（编号：17TD0016）
南充市科技局市校科技战略合作专项（编号：NSMC20170401)
