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2016 ; 60
(6
): 1427-36
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Phenethyl isothiocyanate (PEITC) suppresses prostate cancer cell invasion
epigenetically through regulating microRNA-194
#MMPMID26820911
Zhang C
; Shu L
; Kim H
; Khor TO
; Wu R
; Li W
; Kong AN
Mol Nutr Food Res
2016[Jun]; 60
(6
): 1427-36
PMID26820911
show ga
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.
|*Epigenesis, Genetic
[MESH]
|*Gene Expression Regulation, Neoplastic
[MESH]
|Bone Morphogenetic Protein 1/genetics/metabolism
[MESH]