Unique epigenetic gene profiles define human breast cancers with poor prognosis

Peña-Llopis, Samuel; Wan, Yihong; Martínez, Elisabeth D.

doi:10.18632/oncotarget.13334

Cited by 12 publications

(13 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Bioinformatics analysis based on TCGA was conducted to reveal SUV39H2 and other novel genes (SUV39H1, DNMT3B, EZH2 and AURKB) expressions significantly increase in triple negative (TN) disease and positively associate with high Ki67 levels, TN status and tumor grade. The higher expression of SUV39H2 correlated with shorter survival time [61]. SUV39H2 appears to be associated with more aggressive phenotypes and metastatic biology.…”

Section: Suv39h2 In Breast Cancermentioning

confidence: 86%

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

Li¹,

Zheng²,

Yang³

2019

J. Cancer

View full text Add to dashboard Cite

Epigenetic modifications at the histone level have attracted significant attention because of their roles in tumorigenesis. Suppressor of variegation 3-9 homolog 2 (SUV39H2, also known as KMT1B) is a member of the SUV39 subfamily of lysine methyltransferases (KMTs) that plays a significant role in histone H3-K9 di-/tri-methylation, transcriptional regulation and cell cycle. Overexpressions of SUV39H2 at gene, mRNA and protein levels are known to be associated with a range of cancers: leukemia, lymphomas, lung cancer, breast cancer, colorectal cancer, gastric cancer, hepatocellular cancer and so on. Accumulating evidence indicates that SUV39H2 acts as an oncogene and contributes to the initiation and progression of cancers. It could, therefore, be a promising target for anti-cancer treatment. In this review, we focus on the dysregulation of SUV39H2 in cancers, including its clinical prognostic predictor role, molecular mechanism involved in cancer occurrence and development, relevant inhibitors against cancer, and its epigenetic modification interaction with immunotherapy. A better understanding of the SUV39H2 will be beneficial to the development of molecular-targeted therapies in cancer.

show abstract

Section: Suv39h2 In Breast Cancermentioning

confidence: 86%

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

Li¹,

Zheng²,

Yang³

2019

J. Cancer

View full text Add to dashboard Cite

show abstract

“…Several factors can contribute to transcriptomic variations in breast cancer subtypes, such as differences in the abundance of wild type or mutated transcription factors, mutations that impact the stability and turnover of RNA transcripts, and dysregulation of histone-modifying enzymes [ 13 ]. It is important to determine the relationship between phenotypic subclasses and transcription profiles [ 16 , 64 , 94 ] to elucidate cancer mechanisms and drug targets for more effective treatments.…”

Section: Discussionmentioning

confidence: 99%

“…Several landmark studies have revealed that hyperactivity of the histone-methyltransferase enhancer of zeste 1 and 2 (EZH1, EZH2), which generates the histone PTM H3K27me3, is a feature shared by many types of cancer (recently reviewed in [ 7 ]). In breast cancer, elevated EZH2 has been linked to cell proliferation and metastasis [ 8 , 9 ] and a poor prognosis for breast cancer patients [ 10 – 13 ]. In stem cells and cancer cells, EZH2 generates H3K27me3 marks at nucleosomes (Fig.…”

Section: Introductionmentioning

confidence: 99%

The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells

et al. 2018

View full text Add to dashboard Cite

BackgroundMounting evidence from genome-wide studies of cancer shows that chromatin-mediated epigenetic silencing at large cohorts of genes is strongly linked to a poor prognosis. This mechanism is thought to prevent cell differentiation and enable evasion of the immune system. Drugging the cancer epigenome with small molecule inhibitors to release silenced genes from the repressed state has emerged as a powerful approach for cancer research and drug development. Targets of these inhibitors include chromatin-modifying enzymes that can acquire drug-resistant mutations. In order to directly target a generally conserved feature, elevated trimethyl-lysine 27 on histone H3 (H3K27me3), we developed the Polycomb-based Transcription Factor (PcTF), a fusion activator that targets methyl-histone marks via its N-terminal H3K27me3-binding motif, and co-regulates sets of silenced genes.ResultsHere, we report transcriptome profiling analyses of PcTF-treated breast cancer model cell lines. We identified a set of 19 PcTF-upregulated genes, or PUGs, that were consistent across three distinct breast cancer cell lines. These genes are associated with the interferon response pathway.ConclusionsOur results demonstrate for the first time a chromatin-mediated interferon-related transcriptional response driven by an engineered fusion protein that physically links repressive histone marks with active transcription.Electronic supplementary materialThe online version of this article (10.1186/s12918-018-0608-4) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

“…Several landmark studies have revealed that hyperactivity of the histone-methyltransferase enhancer of zeste 1 and 2 (EZH1, EZH2), which generates the histone PTM H3K27me3, is a feature shared by many types of cancer (recently reviewed in [7] ). In breast cancer, elevated EZH2 has been linked to cell proliferation and metastasis [8,9] and a poor prognosis for breast cancer patients [10][11][12][13] . In stem cells and cancer cells, EZH2 generates H3K27me3 mark at nucleosomes ( Fig.…”

Section: Introductionmentioning

confidence: 99%

The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells

Olney

Nyer

Vargas

et al. 2017

Preprint

View full text Add to dashboard Cite

Disease states, such as breast cancer, arise from the disruption of chromatin, the central DNA-protein structures that package human genetic material. Mounting evidence from genome-wide studies across cancers show that Polycomb-mediated repression of sets of genes, called Polycomb modules, is strongly linked to a poor prognosis. We developed a synthetic transcriptional activator to release silenced genes from the repressed state. The Polycomb-based Transcription Factor (PcTF) is a synthetic effector that accumulates at methyl-histone marks and regulates hundreds of gene targets, including tumor suppressors. We recently reported the activity of PcTF in bone, blood, and brain sarcoma-derived model cell lines. Here, we expand our investigation of PcTF to three breast cancer-derived cell lines. We expressed PcTF in drug-responsive (MCF-7, BT-474) and nonresponsive triple negative (BT-549) breast cancer cell lines. RNA-seq showed that hundreds of genes were up-or down-regulated by PcTF as early as 24 hours after transfection. BT-549, the triple-negative cancer cell line, showed the highest number of PcTF-activated genes. We demonstrate the anti-cancer potential of PcTF by identifying 15 tumor suppressor genes that are upregulated across the three cell types. The data also provide new mechanistic insights into the relationship between chromatin organization and PcTF-mediated regulation of genes. Our results have exciting implications for cancer treatment with engineered biologics.

show abstract

Unique epigenetic gene profiles define human breast cancers with poor prognosis

Cited by 12 publications

References 47 publications

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

The Oncogenic Potential of SUV39H2: A Comprehensive and Perspective View

The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells

The synthetic histone-binding regulator protein PcTF activates interferon genes in breast cancer cells

Contact Info

Product

Resources

About