MicroRNA-34 suppresses breast cancer invasion and metastasis by directly targeting Fra-1

被引：195

作者：

Yang, S. ^{[1
,2
]}

Li, Y. ^{[1
,2
]}

Gao, J. ^{[2
,3
]}

Zhang, T. ^{[1
,2
]}

Li, S. ^{[1
,2
]}

Luo, A. ^{[1
,2
]}

Chen, H. ^{[1
,2
]}

Ding, F. ^{[1
,2
]}

Wang, X. ^{[2
,3
]}

Liu, Z. ^{[1
,2
]}

机构：

[1] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Hosp, Beijing 100021, Peoples R China

[2] Peking Union Med Coll, Beijing 100021, Peoples R China

[3] Chinese Acad Med Sci, Dept Abdominal Surg, Canc Inst & Hosp, Beijing 100021, Peoples R China

来源：

ONCOGENE | 2013年 / 32卷 / 36期

基金：

中国国家自然科学基金;

关键词：

miR-34a; miR-34c; breast cancer; metastasis; NEGATIVE FEEDBACK LOOP; C-MET EXPRESSION; MESENCHYMAL TRANSITION; TUMOR-SUPPRESSOR; GENE-EXPRESSION; DOWN-REGULATION; INHIBITS MIGRATION; MIR-34A; FAMILY; METHYLATION;

D O I：

10.1038/onc.2012.432

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

MicroRNAs have key roles in tumor metastasis. Here, we describe the regulation and function of miR-34a and miR-34c (miR-34a/c) in breast cancer metastasis. Expression analysis verified that miR-34a/c expression is significantly decreased in metastatic breast cancer cells and human primary breast tumors with lymph node metastases. Overexpression of miR-34a/c could inhibit breast cancer cell migration and invasion in vitro and distal pulmonary metastasis in vivo. Further studies revealed that Fos-related antigen 1 (Fra-1 or Fosl1) is a downstream target of miR-34a/c as miR-34a/c bound directly to the 3'untranslated region of Fra-1, subsequently reducing both the mRNA and protein levels of Fra-1. Silencing of Fra-1 recapitulated the effects of miR-34a/c overexpression, whereas enforced expression of Fra-1 reverses the suppressive effects of miR-34a/c. Moreover, significant downregulation of miR-34a in metastatic breast cancer tissues was found to be inversely correlated with Fra-1 expression. Our results demonstrate that miR-34a/c functions as a metastasis suppressor to regulate breast cancer migration and invasion through targeting Fra-1 oncogene and suggest a therapeutic application of miR-34 in breast cancer.

引用

页码：4294 / 4303

页数：10

共 69 条

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