Aberrant histone methylation and the effect of Suv39H1 siRNA on gastric carcinoma

The present study aimed to investigate the involvement of the Suv39H1 histone methyltransferase in the epigenetic changes in the euchromatic promoter in gastric carcinoma. We retrospectively analyzed the protein of Suv39H1 and tri-methylated histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4)...

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Veröffentlicht in:Oncology reports 2014-06, Vol.31 (6), p.2593-2600
Hauptverfasser: CAI, LISHENG, MA, XUDONG, HUANG, YIQUN, ZOU, YONG, CHEN, XINGSHENG
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container_issue 6
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container_title Oncology reports
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creator CAI, LISHENG
MA, XUDONG
HUANG, YIQUN
ZOU, YONG
CHEN, XINGSHENG
description The present study aimed to investigate the involvement of the Suv39H1 histone methyltransferase in the epigenetic changes in the euchromatic promoter in gastric carcinoma. We retrospectively analyzed the protein of Suv39H1 and tri-methylated histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) in 175 cases of gastric carcinoma by immunohistochemistry. Suv39H1 was depleted by siRNA, and cell apoptosis and cell proliferation were assessed by TUNEL and MTT assays, respectively. Histone methylated H3K9 and histone acetylated H3 and H4 were evaluated by western blotting. We found that the expression of Suv39H1 and tri-methylated H3K9 in gastric carcinoma was higher than that in benign gastric diseases (p0.05). Both Suv39H1 and tri-methylated H3K9 were positively correlated with the degree of differentiation, depth of infiltration and lymphatic invasion (p
doi_str_mv 10.3892/or.2014.3135
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We retrospectively analyzed the protein of Suv39H1 and tri-methylated histone H3 lysine 9 (H3K9) and histone H3 lysine 4 (H3K4) in 175 cases of gastric carcinoma by immunohistochemistry. Suv39H1 was depleted by siRNA, and cell apoptosis and cell proliferation were assessed by TUNEL and MTT assays, respectively. Histone methylated H3K9 and histone acetylated H3 and H4 were evaluated by western blotting. We found that the expression of Suv39H1 and tri-methylated H3K9 in gastric carcinoma was higher than that in benign gastric diseases (p&lt;0.05). Tri-methylated H3K4 was similar in both tissue types (p&gt;0.05). Both Suv39H1 and tri-methylated H3K9 were positively correlated with the degree of differentiation, depth of infiltration and lymphatic invasion (p&lt;0.05) in gastric carcinoma. In addition, tri-methylated H3K9 was positively correlated with tumor stage, and node and metastatic statuses (p&lt;0.05). Activation of Suv39H1 and overexpression of H3K9 tri-methylation may play an important role in tumorigenesis. They may be useful as a predictor for poor prognosis in gastric carcinoma. Silencing of the Suv39H1 gene decreased tri-methylated H3K9 and increased histone H3 acetylation, which caused activation of gene transcription, while there was no change in histone H4 acetylation. Depletion of Suv39H1 induced apoptosis and inhibited cell proliferation in the gastric cancer MGC803 cell line, while decreasing BCL-2, pro-caspase-9, pro-caspase-3 and C-myc. Suv39H1 may be a potential gene target for anti-gastric carcinoma therapy.</description><identifier>ISSN: 1021-335X</identifier><identifier>EISSN: 1791-2431</identifier><identifier>DOI: 10.3892/or.2014.3135</identifier><identifier>PMID: 24737085</identifier><language>eng</language><publisher>Greece: D.A. 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Activation of Suv39H1 and overexpression of H3K9 tri-methylation may play an important role in tumorigenesis. They may be useful as a predictor for poor prognosis in gastric carcinoma. Silencing of the Suv39H1 gene decreased tri-methylated H3K9 and increased histone H3 acetylation, which caused activation of gene transcription, while there was no change in histone H4 acetylation. Depletion of Suv39H1 induced apoptosis and inhibited cell proliferation in the gastric cancer MGC803 cell line, while decreasing BCL-2, pro-caspase-9, pro-caspase-3 and C-myc. 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Spandidos</general><general>Spandidos Publications</general><general>Spandidos Publications UK Ltd</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AN0</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope></search><sort><creationdate>20140601</creationdate><title>Aberrant histone methylation and the effect of Suv39H1 siRNA on gastric carcinoma</title><author>CAI, LISHENG ; MA, XUDONG ; HUANG, YIQUN ; ZOU, YONG ; CHEN, XINGSHENG</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c552t-3346b6ba310b54e5372f69b381d3e0963eab70052a656265f050fa440f5149c63</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Aged</topic><topic>Apoptosis</topic><topic>Apoptosis - genetics</topic><topic>Body mass index</topic><topic>Caspase 3 - biosynthesis</topic><topic>Cell growth</topic><topic>Cell Proliferation - genetics</topic><topic>Chromatin</topic><topic>Deoxyribonucleic acid</topic><topic>Development and progression</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>DNA Methylation - genetics</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetics</topic><topic>Female</topic><topic>Gastric cancer</topic><topic>gastric carcinoma</topic><topic>Gene expression</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Genes</topic><topic>Genetic aspects</topic><topic>Health aspects</topic><topic>histone methylation</topic><topic>Histones - metabolism</topic><topic>Humans</topic><topic>Innovations</topic><topic>Leukemia</topic><topic>Male</topic><topic>Metastasis</topic><topic>Methyltransferases</topic><topic>Methyltransferases - antagonists &amp; 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source MEDLINE; Alma/SFX Local Collection; EZB Electronic Journals Library
subjects Aged
Apoptosis
Apoptosis - genetics
Body mass index
Caspase 3 - biosynthesis
Cell growth
Cell Proliferation - genetics
Chromatin
Deoxyribonucleic acid
Development and progression
DNA
DNA methylation
DNA Methylation - genetics
Epigenesis, Genetic
Epigenetics
Female
Gastric cancer
gastric carcinoma
Gene expression
Gene Expression Regulation, Neoplastic
Genes
Genetic aspects
Health aspects
histone methylation
Histones - metabolism
Humans
Innovations
Leukemia
Male
Metastasis
Methyltransferases
Methyltransferases - antagonists & inhibitors
Methyltransferases - genetics
Middle Aged
Molecular targeted therapy
Promoter Regions, Genetic
Properties
Protein expression
Proteins
Proto-Oncogene Proteins c-bcl-2 - biosynthesis
Proto-Oncogene Proteins c-myc - biosynthesis
Repressor Proteins - antagonists & inhibitors
Repressor Proteins - genetics
RNA, Small Interfering - genetics
siRNA interference
Stomach cancer
Stomach Neoplasms - genetics
Stomach Neoplasms - pathology
Suv39H1
title Aberrant histone methylation and the effect of Suv39H1 siRNA on gastric carcinoma
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