An increasing number of studies have demonstrated the important role of
microRNAs (
miRNAs) in modulating
cancer progression and
metastasis, but the mechanisms by which
miRNAs regulate
prostate cancer (PCa)
tumorigenesis remain poorly understood. In the present study, we found that miR-340 may act as a
tumor suppressor based on our finding that it was significantly downregulated in PCa
tumor tissues and cell lines. Moreover, the expression of miR-340 was found to be correlated with the inhibition of cell proliferation, migration and invasion in vitro, and had a suppressive effect on
tumor growth in a xenograft mouse model as well. The suppressive effect of miR-340 overexpression was observed in cell lines DU145 and BPH-1 which express wild-type (WT) p53. However, in the p53-null PC-3 cell line, the suppressive effect was not found, indicating that miR-340 may play a critical role in the p53 pathway. Further investigation revealed that mouse double minute 2 (MDM2), an important regulator of p53, was targeted by miR-340 through the direct binding to the
3'UTR of MDM2, which inhibited MDM2 translation. In addition, miR-340 expression stabilized p53
protein levels which caused an increase in p21 expression but a decrease in the anti‑apoptotic
protein, BCL-2, in the p53 WT cell lines. Moreover, the miR-340-mediated inhibition of cell progression was mitigated by re-expressing MDM2 in the stable miR‑340-overexpressing PCa cell line, which harbors WT p53. Our findings suggest that miR-340 may function as a novel
tumor suppressor in PCa through the MDM2-p53 pathway by directly targeting MDM2, which may be a promising
miRNA-targeted
therapy for PCa.