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Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells
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Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells
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Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells
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Journal Article
Genistein downregulates onco-miR-1260b and upregulates sFRP1 and Smad4 via demethylation and histone modification in prostate cancer cells
2014
Overview
Background:
Recently several microRNAs (miRNAs) have been found to be regulated by genistein in cancer cells. In this study, we focused on the gene regulatory effect of genistein on microRNA and its target genes in prostate cancer (PC).
Methods:
Initially, we investigated the effect of genistein on prostate cancer cells and identified that the expression of miRNA-1260b was decreased by genistein. We performed functional analyses and investigated the relationship between miRNA-1260b expression and prostate cancer patient outcomes. Two target genes (
sFRP1
and
Smad4
) of miR-1260b were identified based on computer algorithm and 3′UTR luciferase assay was carried out to determine direct miRNA regulation of the genes.
Results:
Genistein promoted apoptosis while inhibiting prostate cancer cell proliferation, invasion and TCF reporter activity in PC cells. MiR-1260b was highly expressed in prostate cancer tissues and significantly downregulated by genistein in PC cells. After knocking down miR-1260b, cell proliferation, invasion, migration and TCF reporter activity were decreased in PC cells. Western analysis and 3′UTR luciferase assay showed that the two target genes (
sFRP1
and
Smad4
) were directly regulated by miR-1260b. The expression of sFRP1 and Smad4 was significantly decreased in prostate cancer tissues. Genistein also increased expression of these two genes via DNA demethylation and histone modifications.
Conclusions:
Our data suggest that genistein exerts its anti-tumour effect via downregulation of miR-1260b that targeted
sRRP1
and
Smad4
genes in prostate cancer cells. The expression of sFRP1 and Smad4 was also modulated by genistein via DNA methylation or histone modifications in PC cell lines.
Publisher
Nature Publishing Group UK,Nature Publishing Group
Subject
/ Anticarcinogenic Agents - pharmacology
/ Ataxia Telangiectasia Mutated Proteins - biosynthesis
/ Ataxia Telangiectasia Mutated Proteins - genetics
/ Ataxia Telangiectasia Mutated Proteins - metabolism
/ Biological and medical sciences
/ Biomedical and Life Sciences
/ DNA Methylation - drug effects
/ Gene Expression Regulation, Neoplastic - drug effects
/ Histones
/ Humans
/ In Situ Hybridization, Fluorescence
/ Male
/ miRNA
/ Multiple tumors. Solid tumors. Tumors in childhood (general aspects)
/ Nephrology. Urinary tract diseases
/ Oncology
/ Prostatic Neoplasms - drug therapy
/ Prostatic Neoplasms - genetics
/ Prostatic Neoplasms - metabolism
/ Prostatic Neoplasms - pathology
/ Smad4 Protein - biosynthesis
/ Tumors
/ Tumors of the urinary system
