摘要

Aims Alterations in histone proteins can lead to breast tumorigenesis. Selective histone deacetylase 8 (HDAC8) inhibitors with fewer adverse effects have been developed. A more comprehensive study of alterations and its mechanisms in HDAC8 is required. In this study, we investigated mechanisms of dysregulation of HDAC8 expression and its biological role and pathways in breast cancer. Main methods Alterations in HDAC8 were analyzed in Taiwanese breast cancer patients; and in tissue samples from The Cancer Genome Atlas (TCGA) data set that were derived from Western countries. Knockdown by si-HDAC8, treatment with the HDAC8-specific inhibitor PCI-34051, SRB assays, wound healing, Transwell migration assays, Illumina BeadArray™ arrays and Ingenuity Pathway Analysis (IPA) were performed in breast cancer cells. Key findings HDAC8 mRNA expression was upregulated in paired breast cancer tissue from Taiwanese patients and in paired breast cancer tissues from the TCGA data set. Hypomethylation of promoter regions was significantly correlated with HDAC8 mRNA overexpression in 588 breast cancer patients from the TCGA data set and was associated with poor prognosis in early-stage breast cancer. HDAC8 mRNA overexpression was associated with late stages and tumor progression. Wound healing and Transwell migration assays revealed that knockdown by si-HDAC8 or PCI-34051 treatment significantly inhibited breast cancer cell migration. Knockdown by si-HDAC8, Illumina BeadArray™ arrays and IPA found that ID3 and PTP4A2 pathways were regulated by HDAC8 in cancer cell migration. Significance Hypomethylation of the HDAC8 promoter is correlated with HDAC8 overexpression and breast cancer progression and is a potential prognosis marker and drug target.
原文英語
頁(從 - 到)7-14
頁數8
期刊Life Sciences
151
DOIs
出版狀態已發佈 - 四月 15 2016

指紋

Histone Deacetylases
Cell Movement
Breast Neoplasms
Atlases
Assays
Genes
Genome
Neoplasms
Cells
Tissue
Wound Healing
Messenger RNA
Histone Deacetylase Inhibitors
Genetic Promoter Regions
Histones
Carcinogenesis
Breast
Tumors

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

引用此文

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title = "Alterations in histone deacetylase 8 lead to cell migration and poor prognosis in breast cancer",
abstract = "Aims Alterations in histone proteins can lead to breast tumorigenesis. Selective histone deacetylase 8 (HDAC8) inhibitors with fewer adverse effects have been developed. A more comprehensive study of alterations and its mechanisms in HDAC8 is required. In this study, we investigated mechanisms of dysregulation of HDAC8 expression and its biological role and pathways in breast cancer. Main methods Alterations in HDAC8 were analyzed in Taiwanese breast cancer patients; and in tissue samples from The Cancer Genome Atlas (TCGA) data set that were derived from Western countries. Knockdown by si-HDAC8, treatment with the HDAC8-specific inhibitor PCI-34051, SRB assays, wound healing, Transwell migration assays, Illumina BeadArray™ arrays and Ingenuity Pathway Analysis (IPA) were performed in breast cancer cells. Key findings HDAC8 mRNA expression was upregulated in paired breast cancer tissue from Taiwanese patients and in paired breast cancer tissues from the TCGA data set. Hypomethylation of promoter regions was significantly correlated with HDAC8 mRNA overexpression in 588 breast cancer patients from the TCGA data set and was associated with poor prognosis in early-stage breast cancer. HDAC8 mRNA overexpression was associated with late stages and tumor progression. Wound healing and Transwell migration assays revealed that knockdown by si-HDAC8 or PCI-34051 treatment significantly inhibited breast cancer cell migration. Knockdown by si-HDAC8, Illumina BeadArray™ arrays and IPA found that ID3 and PTP4A2 pathways were regulated by HDAC8 in cancer cell migration. Significance Hypomethylation of the HDAC8 promoter is correlated with HDAC8 overexpression and breast cancer progression and is a potential prognosis marker and drug target.",
keywords = "Breast cancer, Cell migration, DNA methylation, HDAC8, IPA, PCI-34051, Tamoxifen, TCGA",
author = "Hsieh, {Chang Lin} and Ma, {Hon Ping} and Chih-Ming Su and Chang, {Yu Jia} and Hung, {Wan Yu} and Ho, {Yuan Soon} and Huang, {Wei Jan} and Lin, {Ruo Kai}",
year = "2016",
month = "4",
day = "15",
doi = "10.1016/j.lfs.2016.02.092",
language = "English",
volume = "151",
pages = "7--14",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",

}

TY - JOUR

T1 - Alterations in histone deacetylase 8 lead to cell migration and poor prognosis in breast cancer

AU - Hsieh, Chang Lin

AU - Ma, Hon Ping

AU - Su, Chih-Ming

AU - Chang, Yu Jia

AU - Hung, Wan Yu

AU - Ho, Yuan Soon

AU - Huang, Wei Jan

AU - Lin, Ruo Kai

PY - 2016/4/15

Y1 - 2016/4/15

N2 - Aims Alterations in histone proteins can lead to breast tumorigenesis. Selective histone deacetylase 8 (HDAC8) inhibitors with fewer adverse effects have been developed. A more comprehensive study of alterations and its mechanisms in HDAC8 is required. In this study, we investigated mechanisms of dysregulation of HDAC8 expression and its biological role and pathways in breast cancer. Main methods Alterations in HDAC8 were analyzed in Taiwanese breast cancer patients; and in tissue samples from The Cancer Genome Atlas (TCGA) data set that were derived from Western countries. Knockdown by si-HDAC8, treatment with the HDAC8-specific inhibitor PCI-34051, SRB assays, wound healing, Transwell migration assays, Illumina BeadArray™ arrays and Ingenuity Pathway Analysis (IPA) were performed in breast cancer cells. Key findings HDAC8 mRNA expression was upregulated in paired breast cancer tissue from Taiwanese patients and in paired breast cancer tissues from the TCGA data set. Hypomethylation of promoter regions was significantly correlated with HDAC8 mRNA overexpression in 588 breast cancer patients from the TCGA data set and was associated with poor prognosis in early-stage breast cancer. HDAC8 mRNA overexpression was associated with late stages and tumor progression. Wound healing and Transwell migration assays revealed that knockdown by si-HDAC8 or PCI-34051 treatment significantly inhibited breast cancer cell migration. Knockdown by si-HDAC8, Illumina BeadArray™ arrays and IPA found that ID3 and PTP4A2 pathways were regulated by HDAC8 in cancer cell migration. Significance Hypomethylation of the HDAC8 promoter is correlated with HDAC8 overexpression and breast cancer progression and is a potential prognosis marker and drug target.

AB - Aims Alterations in histone proteins can lead to breast tumorigenesis. Selective histone deacetylase 8 (HDAC8) inhibitors with fewer adverse effects have been developed. A more comprehensive study of alterations and its mechanisms in HDAC8 is required. In this study, we investigated mechanisms of dysregulation of HDAC8 expression and its biological role and pathways in breast cancer. Main methods Alterations in HDAC8 were analyzed in Taiwanese breast cancer patients; and in tissue samples from The Cancer Genome Atlas (TCGA) data set that were derived from Western countries. Knockdown by si-HDAC8, treatment with the HDAC8-specific inhibitor PCI-34051, SRB assays, wound healing, Transwell migration assays, Illumina BeadArray™ arrays and Ingenuity Pathway Analysis (IPA) were performed in breast cancer cells. Key findings HDAC8 mRNA expression was upregulated in paired breast cancer tissue from Taiwanese patients and in paired breast cancer tissues from the TCGA data set. Hypomethylation of promoter regions was significantly correlated with HDAC8 mRNA overexpression in 588 breast cancer patients from the TCGA data set and was associated with poor prognosis in early-stage breast cancer. HDAC8 mRNA overexpression was associated with late stages and tumor progression. Wound healing and Transwell migration assays revealed that knockdown by si-HDAC8 or PCI-34051 treatment significantly inhibited breast cancer cell migration. Knockdown by si-HDAC8, Illumina BeadArray™ arrays and IPA found that ID3 and PTP4A2 pathways were regulated by HDAC8 in cancer cell migration. Significance Hypomethylation of the HDAC8 promoter is correlated with HDAC8 overexpression and breast cancer progression and is a potential prognosis marker and drug target.

KW - Breast cancer

KW - Cell migration

KW - DNA methylation

KW - HDAC8

KW - IPA

KW - PCI-34051

KW - Tamoxifen

KW - TCGA

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U2 - 10.1016/j.lfs.2016.02.092

DO - 10.1016/j.lfs.2016.02.092

M3 - Article

VL - 151

SP - 7

EP - 14

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

ER -