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Prostate. 2014 Dec;74(16):1613-21. doi: 10.1002/pros.22878. Epub 2014 Sep 11.

miR-146a functions as a tumor suppressor in prostate cancer by targeting Rac1.

Author information

1
Department of Oncology, No. 3 People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Department of Biochemistry and Molecular Cell Biology, Shanghai Key Laboratory of Tumor Microenvironment and Inflammation, Shanghai Jiao Tong University School of Medicine, Shanghai, China.

Abstract

BACKGROUND:

miR-146a (miR-146a-5p) has been reported to be aberrantly expressed in different types of cancers, the current knowledge about the role of miR-146a in prostate cancer is still limited.

METHODS:

The expression levels of miR-146a in cell lines and tissues were measured by qRT-PCR and in situ hybridization. Effects of miR-146a on cell growth and migration were evaluated by colony formation assay and RTCA assay, respectively. The dual luciferase assay was used to examine the binding between miR-146a and the 3'UTR of potential targets.

RESULTS:

We found that enforced over-expression of miR-146a in prostate cancer cells suppressed whereas knockdown of miR-146a increased anchorage-independent growth, migration, and invasion. Mechanistic studies revealed that miR-146a repressed the expression of Rac1 through binding to its 3'UTR. Consistently, knockdown of Rac1 phenocopied the anti-migration effect of overexpressing miR-146a, and knockdown of Rac1 in miR-146a-silencing cells antagonized the increase in cell motility induced by silencing miR-146a. Furthermore, miR-146a was found to be inversely correlated with Rac1 in human prostate cancer tissues.

CONCLUSIONS:

Our data suggest that miR-146a plays a suppressive role in prostate cancer through down-regulation of Rac1. The miR-146a/Rac1 signaling axis may be a potential therapeutic target to prevent prostate cancer progression.

KEYWORDS:

Rac1; miR-146a; prostate cancer; tumor metastasis

PMID:
25214035
DOI:
10.1002/pros.22878
[Indexed for MEDLINE]

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