Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.

Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome...

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Autores principales:	Yutaka Hashimoto, Marisa Shiina, Shigekatsu Maekawa, Taku Kato, Varahram Shahryari, Priyanka Kulkarni, Pritha Dasgupta, Soichiro Yamamura, Sharanjot Saini, Z Laura Tabatabai, Rajvir Dahiya, Yuichiro Tanaka
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/76ee1a5071504b8785c7c337d3e5510a
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spelling	oai:doaj.org-article:76ee1a5071504b8785c7c337d3e5510a2021-12-02T20:14:04ZSuppressor effect of catechol-O-methyltransferase gene in prostate cancer.1932-620310.1371/journal.pone.0253877https://doaj.org/article/76ee1a5071504b8785c7c337d3e5510a2021-01-01T00:00:00Zhttps://doi.org/10.1371/journal.pone.0253877https://doaj.org/toc/1932-6203Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer. Also, western analyses of prostate cancer cell lines show COMT levels to be minimal in DuPro and DU145 and thus, these cells were used for further analyses. Re-expression of COMT led to suppressed migration ability (wound healing assay) and enhanced apoptosis (flow cytometric analyses), and when challenged with 4-hydroxyestradiol, a marked reduction of cell proliferation (MTT assay) was observed. Xenograft growth in athymic mice also resulted in inhibition due to COMT. As a mechanism, western analyses show cleaved CASP3 and BID were increased whereas XIAP and cIAP2 were reduced due to COMT. As COMT expression is low in prostate cancer, its regulation was determined. Databases identified several miRNAs capable of binding COMT and of these, miR-195 was observed to be increased in prostate cancer according to TCGA. Real-time PCR validated upregulation of miR-195 in clinical prostate cancer specimens as well as DuPro and DU145 and interestingly, luciferase reporter showed miR-195 capable of binding COMT and overexpressing miR-195 could reduce COMT in cells. These results demonstrate COMT to play a protective role by activating the apoptosis pathway and for miR-195 to regulate its expression. COMT may thus be a potential biomarker and gene of interest for therapeutic development for prostate cancer.Yutaka HashimotoMarisa ShiinaShigekatsu MaekawaTaku KatoVarahram ShahryariPriyanka KulkarniPritha DasguptaSoichiro YamamuraSharanjot SainiZ Laura TabatabaiRajvir DahiyaYuichiro TanakaPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 16, Iss 9, p e0253877 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Yutaka Hashimoto Marisa Shiina Shigekatsu Maekawa Taku Kato Varahram Shahryari Priyanka Kulkarni Pritha Dasgupta Soichiro Yamamura Sharanjot Saini Z Laura Tabatabai Rajvir Dahiya Yuichiro Tanaka Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.
description	Catechol-estrogens can cause genetic mutations and to counteract their oncogenicity, the catechol-O-methyltransferase (COMT) gene is capable of neutralizing these reactive compounds. In this study, we determined the functional effects and regulation of COMT in prostate cancer. Both the Cancer Genome Atlas (TCGA) and immunohistochemical analysis of clinical specimens demonstrated a reduction of COMT expression in prostate cancer. Also, western analyses of prostate cancer cell lines show COMT levels to be minimal in DuPro and DU145 and thus, these cells were used for further analyses. Re-expression of COMT led to suppressed migration ability (wound healing assay) and enhanced apoptosis (flow cytometric analyses), and when challenged with 4-hydroxyestradiol, a marked reduction of cell proliferation (MTT assay) was observed. Xenograft growth in athymic mice also resulted in inhibition due to COMT. As a mechanism, western analyses show cleaved CASP3 and BID were increased whereas XIAP and cIAP2 were reduced due to COMT. As COMT expression is low in prostate cancer, its regulation was determined. Databases identified several miRNAs capable of binding COMT and of these, miR-195 was observed to be increased in prostate cancer according to TCGA. Real-time PCR validated upregulation of miR-195 in clinical prostate cancer specimens as well as DuPro and DU145 and interestingly, luciferase reporter showed miR-195 capable of binding COMT and overexpressing miR-195 could reduce COMT in cells. These results demonstrate COMT to play a protective role by activating the apoptosis pathway and for miR-195 to regulate its expression. COMT may thus be a potential biomarker and gene of interest for therapeutic development for prostate cancer.
format	article
author	Yutaka Hashimoto Marisa Shiina Shigekatsu Maekawa Taku Kato Varahram Shahryari Priyanka Kulkarni Pritha Dasgupta Soichiro Yamamura Sharanjot Saini Z Laura Tabatabai Rajvir Dahiya Yuichiro Tanaka
author_facet	Yutaka Hashimoto Marisa Shiina Shigekatsu Maekawa Taku Kato Varahram Shahryari Priyanka Kulkarni Pritha Dasgupta Soichiro Yamamura Sharanjot Saini Z Laura Tabatabai Rajvir Dahiya Yuichiro Tanaka
author_sort	Yutaka Hashimoto
title	Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.
title_short	Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.
title_full	Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.
title_fullStr	Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.
title_full_unstemmed	Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.
title_sort	suppressor effect of catechol-o-methyltransferase gene in prostate cancer.
publisher	Public Library of Science (PLoS)
publishDate	2021
url	https://doaj.org/article/76ee1a5071504b8785c7c337d3e5510a
work_keys_str_mv	AT yutakahashimoto suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT marisashiina suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT shigekatsumaekawa suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT takukato suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT varahramshahryari suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT priyankakulkarni suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT prithadasgupta suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT soichiroyamamura suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT sharanjotsaini suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT zlauratabatabai suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT rajvirdahiya suppressoreffectofcatecholomethyltransferasegeneinprostatecancer AT yuichirotanaka suppressoreffectofcatecholomethyltransferasegeneinprostatecancer
_version_	1718374712990498816

Suppressor effect of catechol-O-methyltransferase gene in prostate cancer.

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