摘要
目的探讨microRNA-451（miR-451）在乳腺癌中的表达及其对乳腺癌细胞MDA-MB-231侵袭能力的影响。
方法收集2014年1月至2014年12月间普通外科行手术切除并经病理检查证实为乳腺浸润性导管癌（IDC）及对应癌旁组织45例，采用实时定量PCR法分别检测miR-451在肿瘤和癌旁组织中的表达，统计分析miR-451表达与患者临床特征间的关系；采用人工合成的miR-451特异性模拟物（miR-451 mimics）转染人乳腺癌MDA-MB-231细胞，采用Transwell侵袭小室试验检测转染miR-451 mimics后MDA-MB-231细胞侵袭能力的变化。通过实时定量PCR、蛋白免疫印记检测转染miR-451 mimics后其下游潜在靶点c-myc及c-myc下游基质金属蛋白酶（MMP）-2、MMP-9表达变化。
结果与对应癌旁组织相比，miR-451在IDC组织中表达水平明显降低（P〈0.05），IDC组织中低水平的miR-451与肿瘤淋巴结转移及高TNM分期有关（P〈0.05）；miR-451 mimics转染MDA-MB-231细胞后可显著抑制乳腺癌细胞的侵袭能力（P〈0.05）；实时定量PCR及蛋白免疫印记结果证实，过表达miR-451后可显著抑制c-myc、MMP-2、MMP-9的表达水平（P〈0.05）。
结论miR-451在IDC组织中表达下调并与患者不良临床病理特征有关，miR-451可能通过下调c-myc/MMP轴的表达来抑制乳腺浸润性导管癌细胞侵袭。
ObjectiveTo investigate the expression of microRNA-451 （miR-451） in female invasive ductal carcinoma （IDC） and its roles in tumor cell invasion.
MethodsForty five IDC tissues and matched tumor adjacent tissues were collected between January and December in 2014. The expressions of miR-451 in tissues were detected by quantitative real-time polymerase chain reaction （qRT-PCR）. The relationship between long noncoding RNA taurine regulated genes 1 （lncRNA-TUG1） and clinical features was analyzed by student-t test. miR-451 mimics was transfected into MDA-MB-231 cells. Transwell assay was used to measure cell invasion ability. The expression of c-myc, a potential target of miR-451, and its downstream genes, matrix metalloproteinase （MMP）-2 and MMP-9 were detected by qRT-PCR and Western-blot.
ResultsThe expression of miR-451 was significantly lower in IDC tissues than in matched tumor adjacent tissues （P〈0.05）. Low expression of miR-451 was positively associated with lymphatic metastasis （P〈0.05） and advanced tumor node metastasis （TNM） stage （P〈0.05）. Up-regulation of miR-451 in MDA-MB-231 cells could significantly suppress cell invasion ability （P〈0.05）. c-myc expression was down-regulated when miR-451 was transfected （P〈0.05）. As downstream genes of c-myc, the expressions of MMP-2 and MMP-9 were suppressed.
ConclusionsmiR-451 is down-regulated in IDC tissues and associated with cell invasion. miR-451 might inhibit IDC progression by inhibiting c-myc/MMP axis.
出处
《中国医师杂志》
CAS
2016年第9期1336-1339,1344,共5页
Journal of Chinese Physician
