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


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2013-09

AUTHORS

S Yang, Y Li, J Gao, T Zhang, S Li, A Luo, H Chen, F Ding, X Wang, Z Liu

ABSTRACT

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. More... »

PAGES

4294

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  • Identifiers

    URI

    http://scigraph.springernature.com/pub.10.1038/onc.2012.432

    DOI

    http://dx.doi.org/10.1038/onc.2012.432

    DIMENSIONS

    https://app.dimensions.ai/details/publication/pub.1033959927

    PUBMED

    https://www.ncbi.nlm.nih.gov/pubmed/23001043


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