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乳腺癌转移的基因异质性可能与miR-21在翻译过程中对TIMP-3的调控有关。

Genetic heterogeneity of breast cancer metastasis may be related to miR-21 regulation of TIMP-3 in translation.

作者信息

Li Jianyi, Zhang Yang, Zhang Wenhai, Jia Shi, Tian Rui, Kang Ye, Ma Yan, Li Dan

机构信息

Department of Breast Surgery, Shengjing Hospital of China Medical University, Shenyang, Liaoning 110004, China.

出版信息

Int J Surg Oncol. 2013;2013:875078. doi: 10.1155/2013/875078. Epub 2013 Jul 10.

Abstract

PURPOSE

MicroRNAs are noncoding RNA molecules that posttranscriptionally regulated expression of target gene and implicate the progress of cancer proliferation, differentiation, and apoptosis. The aim of this study is to determine whether microRNA-21 (miR-21), a specific microRNA implicated in multiple aspects of carcinogenesis, promoted breast cancer metastasis by regulating the tissue inhibitor of metalloproteinase 3 (TIMP-3) gene.

METHODS

miR-21 of serum and tissue from 40 patients (30 patients with breast cancer) were detected by real-time quantitative reverse transcriptase polymerase chain reaction (RT-qPCR). TIMP-3 of tissue from the patient was tested by real-time RT-qPCR. Protein expression of TIMP-3 was evaluated by western blotting. Correlation analysis was performed between miR-21 and TIMP-3.

RESULTS

Of the 40 samples from tissue and serum analyzed, the miR-21 expression was significantly higher in high invasion metastasis group (HIMG) that in low invasion metastasis group (LIMG); the latter was higher than that in normal group (NG). Additionally, the TIMP-3 expression was significantly lower in HIMG than in LIMG; the latter was lower than that in NG. There was significantly inverse correlation between miR-21 and TIMP-3 extracted from tissue.

CONCLUSION

Our data suggest that miR-21 could promote metastasis in breast cancer via the regulation of TIMP3 translation, and there was consistency between miR-21 of serum and miR-21 in tissue.

摘要

目的

微小RNA是非编码RNA分子,可在转录后调节靶基因的表达,并与癌症增殖、分化和凋亡进程相关。本研究旨在确定微小RNA-21(miR-21)这种参与致癌作用多个方面的特定微小RNA是否通过调节金属蛋白酶组织抑制剂3(TIMP-3)基因来促进乳腺癌转移。

方法

采用实时定量逆转录聚合酶链反应(RT-qPCR)检测40例患者(30例乳腺癌患者)血清和组织中的miR-21。采用实时RT-qPCR检测患者组织中的TIMP-3。通过蛋白质印迹法评估TIMP-3的蛋白表达。对miR-21和TIMP-3进行相关性分析。

结果

在分析的40份组织和血清样本中,高侵袭转移组(HIMG)的miR-21表达显著高于低侵袭转移组(LIMG);低侵袭转移组高于正常组(NG)。此外,HIMG中TIMP-3的表达显著低于LIMG;LIMG低于NG。从组织中提取的miR-21与TIMP-3之间存在显著负相关。

结论

我们的数据表明,miR-21可通过调节TIMP3的翻译来促进乳腺癌转移,血清中的miR-21与组织中的miR-21具有一致性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/826a/3723359/fe72e4f73bf0/IJSO2013-875078.001.jpg

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