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Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer

Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs). In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa) and target pathways. Using miRNA micro...

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Autores principales: Chiyomaru, Takeshi, Yamamura, Soichiro, Fukuhara, Shinichiro, Hidaka, Hideo, Majid, Shahana, Saini, Sharanjot, Arora, Sumit, Deng, Guoren, Shahryari, Varahram, Chang, Inik, Tanaka, Yuichiro, Tabatabai, Z. Laura, Enokida, Hideki, Seki, Naohiko, Nakagawa, Masayuki, Dahiya, Rajvir
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595226/
https://www.ncbi.nlm.nih.gov/pubmed/23554959
http://dx.doi.org/10.1371/journal.pone.0058929
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author Chiyomaru, Takeshi
Yamamura, Soichiro
Fukuhara, Shinichiro
Hidaka, Hideo
Majid, Shahana
Saini, Sharanjot
Arora, Sumit
Deng, Guoren
Shahryari, Varahram
Chang, Inik
Tanaka, Yuichiro
Tabatabai, Z. Laura
Enokida, Hideki
Seki, Naohiko
Nakagawa, Masayuki
Dahiya, Rajvir
author_facet Chiyomaru, Takeshi
Yamamura, Soichiro
Fukuhara, Shinichiro
Hidaka, Hideo
Majid, Shahana
Saini, Sharanjot
Arora, Sumit
Deng, Guoren
Shahryari, Varahram
Chang, Inik
Tanaka, Yuichiro
Tabatabai, Z. Laura
Enokida, Hideki
Seki, Naohiko
Nakagawa, Masayuki
Dahiya, Rajvir
author_sort Chiyomaru, Takeshi
collection PubMed
description Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs). In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa) and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1) and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as ‘Pathways in cancer’, ‘Jak-STAT signaling pathway’, and ‘Wnt signaling pathway’. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3′ UTR of several target genes (such as RAC1, EGFR and EP300) that are components of ‘Pathways in cancer’. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa.
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spelling pubmed-35952262013-04-02 Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer Chiyomaru, Takeshi Yamamura, Soichiro Fukuhara, Shinichiro Hidaka, Hideo Majid, Shahana Saini, Sharanjot Arora, Sumit Deng, Guoren Shahryari, Varahram Chang, Inik Tanaka, Yuichiro Tabatabai, Z. Laura Enokida, Hideki Seki, Naohiko Nakagawa, Masayuki Dahiya, Rajvir PLoS One Research Article Genistein has been shown to inhibit cancers both in vitro and in vivo, by altering the expression of several microRNAs (miRNAs). In this study, we focused on tumor suppressor miRNAs regulated by genistein and investigated their function in prostate cancer (PCa) and target pathways. Using miRNA microarray analysis and real-time RT-PCR we observed that miR-574-3p was significantly up-regulated in PCa cells treated with genistein compared with vehicle control. The expression of miR-574-3p was significantly lower in PCa cell lines and clinical PCa tissues compared with normal prostate cells (RWPE-1) and adjacent normal tissues. Low expression level of miR-574-3p was correlated with advanced tumor stage and higher Gleason score in PCa specimens. Re-expression of miR-574-3p in PCa cells significantly inhibited cell proliferation, migration and invasion in vitro and in vivo. miR-574-3p restoration induced apoptosis through reducing Bcl-xL and activating caspase-9 and caspase-3. Using GeneCodis software analysis, several pathways affected by miR-574-3p were identified, such as ‘Pathways in cancer’, ‘Jak-STAT signaling pathway’, and ‘Wnt signaling pathway’. Luciferase reporter assays demonstrated that miR-574-3p directly binds to the 3′ UTR of several target genes (such as RAC1, EGFR and EP300) that are components of ‘Pathways in cancer’. Quantitative real-time PCR and Western analysis showed that the mRNA and protein expression levels of the three target genes in PCa cells were markedly down-regulated with miR-574-3p. Loss-of-function studies demonstrated that the three target genes significantly affect cell proliferation, migration and invasion in PCa cell lines. Our results show that genistein up-regulates tumor suppressor miR-574-3p expression targeting several cell signaling pathways. These findings enhance understanding of how genistein regulates with miRNA in PCa. Public Library of Science 2013-03-12 /pmc/articles/PMC3595226/ /pubmed/23554959 http://dx.doi.org/10.1371/journal.pone.0058929 Text en © 2013 Chiyomaru et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Chiyomaru, Takeshi
Yamamura, Soichiro
Fukuhara, Shinichiro
Hidaka, Hideo
Majid, Shahana
Saini, Sharanjot
Arora, Sumit
Deng, Guoren
Shahryari, Varahram
Chang, Inik
Tanaka, Yuichiro
Tabatabai, Z. Laura
Enokida, Hideki
Seki, Naohiko
Nakagawa, Masayuki
Dahiya, Rajvir
Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer
title Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer
title_full Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer
title_fullStr Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer
title_full_unstemmed Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer
title_short Genistein Up-Regulates Tumor Suppressor MicroRNA-574-3p in Prostate Cancer
title_sort genistein up-regulates tumor suppressor microrna-574-3p in prostate cancer
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3595226/
https://www.ncbi.nlm.nih.gov/pubmed/23554959
http://dx.doi.org/10.1371/journal.pone.0058929
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