Abstract
SCOPE: Tumor metastasis greatly contributes to the mortality of prostate cancer. The glucosinolate-derived phenethyl isothiocyanate (PEITC) has been widely documented to reduce the risk of prostate cancer by modulating multiple biologically relevant processes. Emerging evidence suggests that PEITC may exert its anti-cancer effects through epigenetic mechanisms including microRNAs. Altered levels of miRNA have been linked to tumor malignancy due to their capacity to regulate functional gene expression in carcinogenesis. Here, we assessed the effects of PEITC on miRNA expression which is related to PCa cell invasiveness. METHODS AND RESULTS: Utilizing oligonucleotide microarray first identified the most affected miRNAs in LNCaP cells after PEITC treatment. Several top altered miRNAs were further validated using quantitative PCR. Interestingly, overexpression of miR-194 suppressed PC3 cell invasion in matrigel-coated Transwell chambers. Bone morphogenetic protein 1 (BMP1) was shown to be a direct target of miR-194. Downregulation of BMP1 by miR-194 or PEITC led to decreased expression of key oncogenic matrix metalloproteinases, MMP2 and MMP9. This in turn resulted in the suppression of tumor invasion. CONCLUSION: Our results indicate that miR-194 downregulates the expression of oncogenic MMP2 and MMP9 by targeting BMP1, which suggests a potential new mechanistic target by which PEITC suppresses prostate cancer cell invasiveness.