Tumor suppressive miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells
Although prostate cancer (CaP) is the most frequently diagnosed malignant tumor in American men, the mechanisms underlying the development and progression of CaP remain largely unknown. Recent studies have shown that downregulation of the microRNA miR-124 occurs in several types of human cancer, sug...
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Veröffentlicht in: | Oncogene 2013-08, Vol.32 (35), p.4130-4138 |
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Zusammenfassung: | Although prostate cancer (CaP) is the most frequently diagnosed malignant tumor in American men, the mechanisms underlying the development and progression of CaP remain largely unknown. Recent studies have shown that downregulation of the microRNA
miR-124
occurs in several types of human cancer, suggesting a tumor suppressive function of
miR-124
. Until now, however, it has been unclear whether
miR-124
is associated with CaP. In the present study, we completed a series of experiments to understand the functional role of
miR-124
in CaP. We detected the expression level of
miR-124
in clinical CaP tissues, evaluated the influence of
miR-124
on the growth of CaP cells and investigated the mechanism underlying the dysregulation of
miR-124
. We found that (i)
miR-124
directly targets the androgen receptor (AR) and subsequently induces an upregulation of p53; (ii)
miR-124
is significantly downregulated in malignant prostatic cells compared to benign cells, and DNA methylation causes the reduced expression of
miR-124
; and (iii)
miR-124
can inhibit the growth of CaP cells
in vitro
and
in vivo
. Data from this study revealed that loss of
miR-124
expression is a common event in CaP, which may contribute to the pathogenesis of CaP. Our studies also suggest that
miR-124
is a potential tumor suppressive gene in CaP, and restoration of
miR-124
expression may represent a novel strategy for CaP therapy. |
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ISSN: | 0950-9232 1476-5594 |
DOI: | 10.1038/onc.2012.425 |