Tumor suppressive miR-124 targets androgen receptor and inhibits proliferation of prostate cancer cells

Abstract

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 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 a upregulation of p53; ii) miR-124 is significantly down-regulated in malignant prostatic cells compared to that in 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 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.

The expression of miR-124 increases in aged skin to cause cell senescence and it decreases in squamous cell carcinoma

“…The current authors previously reported that the miR-124 expression was down-regulated in cutaneous SCC (14), which results in the overexpression of ERK as a target molecule and subsequent cell proliferation. miR-124 was also reported to be involved in the carcinogenesis of various cancers such as glioblastoma, gastric cancer, hepatocellular cancer, breast cancer, and prostate cancer (15)(16)(17)(18)(19), indicating that miR-124 is a key miRNA in carcinogenesis.…”

PACE4 Undergoes an Oncogenic Alternative Splicing Switch in Cancer

“…2A). The PACE4-targeting miRNA regulatory sites predicted by TargetScan for miR-21, which is overexpressed in prostate cancer (19), and miR-124, a tumor suppressor that is downregulated in prostate cancer (20), were all absent from the transcript after 3 0 UTR replacement (14) ( Fig. 2A).…”

Association of the pri-miR-124-1 rs531564 polymorphism with cancer risk: A meta-analysis

“…Shi et al (25) demonstrated that miR-124 was commonly reduced in prostate cancer, which directly targets the androgen receptor and subsequently induces an increased expression of the tumor suppressive gene, p53. Furuta et al (26) suggested cyclin-dependent kinase 6 (CDK6) as a possible target for miR-124, which was a key modulator of cell cycle and differentiation.…”