Clustered DNA methylation changes in polycomb target genes in early-stage liver cancer

Chen, Yao Li; Ko, Chih Jan; Lin, Ping; Chuang, Wan Ling; Hsu, Chia Chen; Chu, Pei Yi; Pai, Mei Yu; Chang, Chun; Kuo, Ming Han; Chu, Yi Ru; Tung, Chun Hsin; Huang, Tim H-M.; Leu, Yu Wei; Hsiao, Shu Huei

doi:10.1016/j.bbrc.2012.07.084

Cited by 14 publications

(5 citation statements)

References 17 publications

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“…This phenomenon has previously been described in colon cancer cells (46). Numerous groups have shown links between DNA methylation and PcG genes (19)(20)(21); however, these studies have been limited to in vitro cell line work or in silico analysis of methylated genes discovered from tissues along with overlapping polycomb marks in embryonic stem cells. For example, previous in vitro work has described increased methylation of PrEC polycomb-marked genes in the prostate cancer cell line PC3 (19).…”

Section: Discussionmentioning

confidence: 66%

Altered DNA Methylation Landscapes of Polycomb-Repressed Loci Are Associated with Prostate Cancer Progression and ERG Oncogene Expression in Prostate Cancer

Kron

Trudel

Pethe

et al. 2013

Clinical Cancer Research

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Purpose: To assess differentially methylated "landscapes" according to prostate cancer Gleason score (GS) and ERG oncogene expression status, and to determine the extent of polycomb group (PcG) target gene involvement, we sought to assess the genome-wide DNA methylation profile of prostate cancer according to Gleason score and ERG expression.Experimental Design: Genomic DNA from 39 prostate cancer specimens was hybridized to CpG island microarrays through differential methylation hybridization. We compared methylation profiles between Gleason score and ERG expression status as well as Gleason score stratified by ERG expression status. In addition, we compared results from our dataset to publicly available datasets of histone modifications in benign prostate cells.Results: We discovered hundreds of distinct differentially methylated regions (DMR) associated with increasing Gleason score and ERG. Furthermore, the number of DMRs associated with Gleason score was greatly expanded by stratifying samples into ERG-positive versus ERG-negative, with ERG-positive/GSassociated DMRs being primarily hypermethylated as opposed to hypomethylated. Finally, we found that there was a significant overlap between either Gleason score-related or ERG-hypermethylated DMRs and distinct regions in benign epithelial cells that have PcG signatures (H3K27me3, SUZ12) and lack active gene expression signatures (H3K4me3, RNA pol II).Conclusions: This work defines methylation landscapes of prostate cancer according to Gleason score, and suggests that initiating genetic events may influence the prostate cancer epigenome, which is further perturbed as prostate cancer progresses. Moreover, CpG islands with silent chromatin signatures in benign cells are particularly susceptible to prostate cancer-related hypermethylation.

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Section: Discussionmentioning

confidence: 66%

Altered DNA Methylation Landscapes of Polycomb-Repressed Loci Are Associated with Prostate Cancer Progression and ERG Oncogene Expression in Prostate Cancer

Kron

Trudel

Pethe

et al. 2013

Clinical Cancer Research

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“…Recently hypermethylated in cancer 1 (HIC1) gene has been considered as a candidate tumor suppressor gene [4]. Studies have shown that in most of the common human cancer types, HIC1 is usually epigenetically silenced [4], such as in renal cell carcinoma [5], hepatocellular carcinoma [6,7], pancreatic cancer [8], prostate cancers [9,10] and hyperparathyroid tumors [11], etc. The metastasis of cancer is generally associated with the methylation of HIC1 promoter [12].…”

Section: Introductionmentioning

confidence: 99%

Zwitterion-functionalized dendrimer-entrapped gold nanoparticles for serum-enhanced gene delivery to inhibit cancer cell metastasis

et al. 2019

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“…Hypermethylated in cancer-1 ( HIC1 ), a tumor suppressor gene essential to mammalian development [4], is located in the chromosomal regions 17p13.3, and is telomeric to the TP53. In many different human cancers (including prostate [5–7], hepatocellular [8, 9], pancreatic [10], renal cell carcinoma [11], breast cancers [12] and esophageal cancers [13], HIC1 is epigenetically inactivated but not mutated [14]. The methylation status of the HIC1 promoter is also associated with tumorigenesis and poor survival in patients with medulloblastomas [15].…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma

Zhang

Lin

et al. 2016

Oncotarget

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Hypermethylation leading to the loss of hypermethylated in cancer-1 (HIC1) gene expression occurs in many different types of human cancer. HIC1 is a transcriptional repressor that directly binds to the promoter region of NAD-dependent deacetylase sirtuin-1 (SIRT1). SIRT1 functions in cell growth, is anti-apoptotic, protect neurons, functions in senescence, and regulates energy restriction. Epigenetic modification and dysregulation affecting the HIC1/SIRT1 axis is potentially important for the development of malignancies. However, the importance of HIC1 expression in the development of papillary thyroid carcinoma, especially in Chinese patients, is uncertain. Therefore, we assessed the level of methylation in the HIC1 promoter and the mRNA and protein expression levels of HIC1 and SIRT1 in human thyroid papillary carcinoma and tumor adjacent control tissues. The demethylation reagent 5-aza-2′-deoxyctidine (5-aza-dc) and an HIC1 overexpression plasmid were used to manipulate the HIC1/SIRT1 pathway, and the effects on cell senescence, apoptosis, and cell cycle progression were assessed. Compared to normal thyroid tissue, thyroid tumors had lower expression of HIC1 and higher SIRT1 expression. The level of HIC1 methylation was also higher in thyroid carcinoma tissues than adjacent tissues. HIC1 expression was closely correlated with patient age and tumor progression. Restoration of HIC1 expression through an overexpression plasmid or 5-aza-dC treatment reduced SIRT1 expression and cell proliferation, and led to senescence, cell cycle arrest, and apoptosis. Aberrant expression of HIC1/SIRT1 and hypermethylation of the HIC1 promoter may be critical for the development and progression of papillary thyroid cancer.

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Clustered DNA methylation changes in polycomb target genes in early-stage liver cancer

Cited by 14 publications

References 17 publications

Altered DNA Methylation Landscapes of Polycomb-Repressed Loci Are Associated with Prostate Cancer Progression and ERG Oncogene Expression in Prostate Cancer

Altered DNA Methylation Landscapes of Polycomb-Repressed Loci Are Associated with Prostate Cancer Progression and ERG Oncogene Expression in Prostate Cancer

Zwitterion-functionalized dendrimer-entrapped gold nanoparticles for serum-enhanced gene delivery to inhibit cancer cell metastasis

Hypermethylation of the HIC1 promoter and aberrant expression of HIC1/SIRT1 contribute to the development of thyroid papillary carcinoma

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