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https://www.readbyqxmd.com/read/29792595/brg1-governs-glucocorticoid-receptor-interactions-with-chromatin-and-pioneer-factors-across-the-genome
#1
Jackson A Hoffman, Kevin W Trotter, James M Ward, Trevor K Archer
The Glucocorticoid Receptor (GR) alters transcriptional activity in response to hormones by interacting with chromatin at GR binding sites (GBSs) throughout the genome. Our work in human breast cancer cells identifies three classes of GBSs with distinct epigenetic characteristics and reveals that BRG1 interacts with GBSs prior to hormone exposure. The GBSs pre-occupied by BRG1 are more accessible and transcriptionally active than other GBSs. BRG1 is required for a proper and robust transcriptional hormone response and knockdown of BRG1 blocks recruitment of the pioneer factors FOXA1 and GATA3 to GBSs...
May 24, 2018: ELife
https://www.readbyqxmd.com/read/29780354/targeting-the-metastatic-bone-microenvironment-by-micrornas
#2
REVIEW
Marie-Therese Haider, Hanna Taipaleenmäki
Bone metastases are a common and devastating feature of late-stage breast cancer. Metastatic bone disease is a consequence of disturbed bone remodeling due to pathological interactions between cancer cells and the bone microenvironment (BME). In the BME, breast cancer cells severely alter the balanced bone formation and bone resorption driven by osteoblasts and osteoclasts. The complex cellular cross talk in the BME is governed by secreted molecules, signaling pathways and epigenetic cues including non-coding RNAs...
2018: Frontiers in Endocrinology
https://www.readbyqxmd.com/read/29778718/nimbolide-epigenetically-regulates-autophagy-and-apoptosis-in-breast-cancer
#3
Venkatesh Pooladanda, Soumya Bandi, Sandhya Rani Mondi, Krishna Mohan Gottumukkala, Chandraiah Godugu
Autophagy is a critical regulator of cellular homeostasis and its dysregulation often results in various disease manifestations, including cancer. Nimbolide, an active chemical constituent of neem (Azadirachta indica) exhibits potent anticancer effects. Although, nimbolide mediated apoptosis activation in breast cancer cells is well known. Nevertheless, its role in autophagy induction mechanism and epigenetic alteration is not explored previously. Our current study intended to bridge the gaps in the existing research by exploring the potential of nimbolide in inducing autophagy, which could counter regulate the transformations in breast cancer...
May 17, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/29777275/overexpression-of-abcb4-contributes-to-acquired-doxorubicin-resistance-in-breast-cancer-cells-in-vitro
#4
Jia-Feng Huang, Chun-Jie Wen, Guo-Zhi Zhao, Yi Dai, Ying Li, Lan-Xiang Wu, Hong-Hao Zhou
PURPOSE: Doxorubicin is one of the most active agents in the first-line therapy for metastatic breast cancer, but its utility is partially limited by the frequent emergence of doxorubicin resistance. In this study, we aimed to investigate the role of ATP-binding cassette sub-family B, member 4 (ABCB4) in acquired doxorubicin resistance in breast cancer cells, as well as its potential mechanism. METHODS: In doxorubicin-sensitive and -resistant breast cancer cell lines MCF-7 and MDA-MB-231, the expression levels of ABCB4 were detected using real-time quantitative PCR and Western blot analysis, the DNA methylation and histone acetylation status of ABCB4 gene were investigated by bisulfite-sequencing PCR (BSP) and chromatin immunoprecipitation (ChIP) assays, and the doxorubicin sensitivity and intracellular doxorubicin accumulation were observed using cell cytotoxicity assay and flow cytometry...
May 18, 2018: Cancer Chemotherapy and Pharmacology
https://www.readbyqxmd.com/read/29764806/temporal-efficacy-of-a-sulforaphane-based-broccoli-sprout-diet-in-prevention-of-breast-cancer-through-modulation-of-epigenetic-mechanisms
#5
Yuanyuan Li, Phillip Buckhaults, Shizhao Li, Trygve O Tollefsbol
Breast cancer is the most common cancer and the second leading cause of cancer death among women. An important risk factor for breast cancer is individual genetic background which is initially generated early in human life; for example, during the processes of embryogenesis and fetal development in utero. Bioactive dietary components such as sulforaphane (SFN), an isothiocyanate from cruciferous vegetables including broccoli sprouts (BSp), cabbage and kale, has been shown to reduce the risk of developing many common cancers through regulation of epigenetic mechanisms...
May 15, 2018: Cancer Prevention Research
https://www.readbyqxmd.com/read/29759486/inhibition-of-hdacs-epha2-signaling-axis-with-ww437-demonstrates-promising-preclinical-antitumor-activity-in-breast-cancer
#6
Tao Zhang, Jingjie Li, Xiaojun Ma, Yang Yang, Wei Sun, Wangrui Jin, Lei Wang, Yuan He, Feifei Yang, Zhengfang Yi, Yingqi Hua, Mingyao Liu, Yihua Chen, Zhengdong Cai
Histone deacetylase inhibitors (HDACi) are small molecules targeting epigenetic enzymes approved for hematologic neoplasms, which have also demonstrated clinical activities in solid tumors. In our present study, we screened our internal compound library and discovered a novel HDACi, WW437, with potent anti-breast cancer ability in vitro and in vivo. WW437 significantly inhibited phosphorylated EphA2 and EphA2 expression. Further study demonstrated WW437 blocked HDACs-EphA2 signaling axis in breast cancer. In parallel, we found that EphA2 expression positively correlates with breast cancer progression; and combined use of WW437 and an EphA2 inhibitor (ALW-II-41-27) exerted more remarkable effect on breast cancer growth than either drug alone...
May 11, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29759441/nuclear-organization-mediates-cancer-compromised-genetic-and-epigenetic-control
#7
REVIEW
Sayyed K Zaidi, Andrew Fritz, Kirsten Tracy, Jonathan Gordon, Coralee Tye, Joseph Boyd, Andre Van Wijnen, Jeffrey Nickerson, Anthony Imbalzano, Jane Lian, Janet Stein, Gary Stein
Nuclear organization is functionally linked to genetic and epigenetic regulation of gene expression for biological control and is modified in cancer. Nuclear organization supports cell growth and phenotypic properties of normal and cancer cells by facilitating physiologically responsive interactions of chromosomes, genes and regulatory complexes at dynamic three-dimensional microenvironments. We will review nuclear structure/function relationships that include: 1. Epigenetic bookmarking of genes by phenotypic transcription factors to control fidelity and plasticity of gene expression as cells enter and exit mitosis; 2...
May 9, 2018: Advances in Biological Regulation
https://www.readbyqxmd.com/read/29757984/integrative-bioinformatics-and-functional-analyses-of-geo-encode-and-tcga-reveal-fadd-as-a-direct-target-of-the-tumor-suppressor-brca1
#8
Dinh-Duc Nguyen, Dong Gyu Lee, Sinae Kim, Keunsoo Kang, Je-Keun Rhee, Suhwan Chang
BRCA1 is a multifunctional tumor suppressor involved in several essential cellular processes. Although many of these functions are driven by or related to its transcriptional/epigenetic regulator activity, there has been no genome-wide study to reveal the transcriptional/epigenetic targets of BRCA1. Therefore, we conducted a comprehensive analysis of genomics/transcriptomics data to identify novel BRCA1 target genes. We first analyzed ENCODE data with BRCA1 chromatin immunoprecipitation (ChIP)-sequencing results and identified a set of genes with a promoter occupied by BRCA1...
May 14, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29743726/dramatic-dysbalancing-of-the-wnt-pathway-in-breast-cancers
#9
Alexey Koval, Vladimir L Katanaev
Wnt signaling is important for breast development and remodeling during pregnancy and lactation. Epigenetic modifications change expression levels of components of the Wnt pathway, underlying oncogenic transformation. However, no clear Wnt component increasing expression universally across breast cancer (BC) or its most Wnt-dependent triple-negative BC (TNBC) subgroup has been identified, delaying development of targeted therapies. Here we perform network correlation analysis of expression of >100 Wnt pathway components in hundreds of healthy and cancerous breast tissues...
May 9, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29741645/lsd1-coordinates-with-the-sin3a-hdac-complex-and-maintains-sensitivity-to-chemotherapy-in-breast-cancer
#10
Yang Yang, Wei Huang, Rongfang Qiu, Ruiqiong Liu, Yi Zeng, Jie Gao, Yu Zheng, Yongqiang Hou, Shuang Wang, Wenqian Yu, Shuai Leng, Dandan Feng, Yan Wang
Lysine-specific demethylase 1 (LSD1) was the first histone demethylase identified as catalysing the removal of mono- and di-methylation marks on histone H3-K4. Despite the potential broad action of LSD1 in transcription regulation, recent studies indicate that LSD1 may coordinate with multiple epigenetic regulatory complexes including CoREST/HDAC complex, NuRD complex, SIRT1, and PRC2, implying complicated mechanistic actions of this seemingly simple enzyme. Here, we report that LSD1 is also an integral component of the SIN3A/HDAC complex...
May 7, 2018: Journal of Molecular Cell Biology
https://www.readbyqxmd.com/read/29740925/metformin-directly-targets-the-h3k27me3-demethylase-kdm6a-utx
#11
Elisabet Cuyàs, Sara Verdura, Laura Llorach-Pares, Salvador Fernández-Arroyo, Fedra Luciano-Mateo, Noemí Cabré, Jan Stursa, Lukas Werner, Begoña Martin-Castillo, Benoit Viollet, Jiri Neuzil, Jorge Joven, Alfons Nonell-Canals, Melchor Sanchez-Martinez, Javier A Menendez
Metformin, the first drug chosen to be tested in a clinical trial aimed to target the biology of aging per se, has been clinically exploited for decades in the absence of a complete understanding of its therapeutic targets or chemical determinants. We here outline a systematic chemoinformatics approach to computationally predict biomolecular targets of metformin. Using several structure- and ligand-based software tools and reference databases containing 1,300,000 chemical compounds and more than 9,000 binding sites protein cavities, we identified 41 putative metformin targets including several epigenetic modifiers such as the member of the H3K27me3-specific demethylase subfamily, KDM6A/UTX...
May 8, 2018: Aging Cell
https://www.readbyqxmd.com/read/29733910/the-contribution-of-cholesterol-and-epigenetic-changes-to-the-pathophysiology-of-breast-cancer
#12
REVIEW
Maliha T Munir, Christopher Ponce, Catherine A Powell, Kaiser Tarafdar, Teru Yanagita, Mahua Choudhury, Lauren S Gollahon, Shaikh M Rahman
Breast cancer is one of the most commonly diagnosed cancers in women. Accumulating evidence suggests that cholesterol plays an important role in the development of breast cancer. Even though the mechanistic link between these two factors is not well understood, one possibility is that dysregulated cholesterol metabolism may affect lipid raft and membrane fluidity and can promote tumor development. Current studies have shown oxysterol 27-hydroxycholesterol (27-HC) as a critical regulator of cholesterol and breast cancer pathogenesis...
May 4, 2018: Journal of Steroid Biochemistry and Molecular Biology
https://www.readbyqxmd.com/read/29731982/gene-specific-methylation-profiles-in-brca-mutation-positive-and-brca-mutation-negative-male-breast-cancers
#13
Piera Rizzolo, Valentina Silvestri, Virginia Valentini, Veronica Zelli, Ines Zanna, Giovanna Masala, Simonetta Bianchi, Domenico Palli, Laura Ottini
Male breast cancer (MBC) is a rare disease. Due to its rarity, MBC research and clinical approach are mostly based upon data derived from female breast cancer (FBC). Increasing evidence indicate that on molecular level MBC may be an heterogeneous disease different from FBC. In order to investigate whether epigenetic signatures could define molecular subgroups of MBCs, we performed promoter methylation analysis of genes involved in signal transduction and hormone signalling in BRCA1/2 mutation-positive and -negative MBCs...
April 13, 2018: Oncotarget
https://www.readbyqxmd.com/read/29731905/effect-of-high-wdr5-expression-on-the-hepatocellular-carcinoma-prognosis
#14
Zhoujun Cui, Hongbo Li, Feng Liang, Cuiling Mu, Yuhua Mu, Xuegong Zhang, Jundong Liu
WD repeat domain 5 (WDR5) serves an important role in various biological functions through the epigenetic regulation of gene transcription. Aberrant expression of WDR5 has been observed in various types of human cancer, including prostate cancer, breast cancer and leukemia. However, the role of WDR5 expression and its clinical implications in hepatocellular carcinoma (HCC) remain largely unknown. The present study investigated the WDR5 expression pattern in HCC. It was demonstrated that the mRNA and protein levels of WDR5 were upregulated in HCC cancer tissues compared with normal adjacent tissues using reverse transcription-quantitative polymerase chain reaction and western blotting...
May 2018: Oncology Letters
https://www.readbyqxmd.com/read/29721098/capg-enhances-breast-cancer-metastasis-by-competing-with-prmt5-to-modulate-stc-1-transcription
#15
Sheng Huang, Yayun Chi, Yi Qin, Ziliang Wang, Bingqiu Xiu, Yonghui Su, Rong Guo, Liang Guo, Hefen Sun, Chujia Zeng, Shuling Zhou, Xin Hu, Sheng Liu, Zhimin Shao, Zhaohui Wu, Wei Jin, Jiong Wu
Macrophage-capping protein (CAPG) has been shown to promote cancer cell metastasis, although the mechanism remains poorly understood. Methods: Breast cancer (BC) tissue microarray was used to test the role of CAPG in the prognosis of BC patients. Xenograft mice model was used to validate the metastasis promotion role of CAPG in vivo. Gene expression array, chromatin immunoprecipitation and luciferase report assay were performed to search for the target genes of CAPG. Protein immunoprecipitation, MS/MS analysis, tissue microarray and histone methyltransferase assay were used to explore the mechanism of CAPG regulating stanniocalcin 1 (STC-1) transcription...
2018: Theranostics
https://www.readbyqxmd.com/read/29721079/dna-methylation-signatures-predicting-bevacizumab-efficacy-in-metastatic-breast-cancer
#16
Simon Peter Gampenrieder, Gabriel Rinnerthaler, Hubert Hackl, Walter Pulverer, Andreas Weinhaeusel, Suzana Ilic, Clemens Hufnagl, Cornelia Hauser-Kronberger, Alexander Egle, Angela Risch, Richard Greil
Background: Biomarkers predicting response to bevacizumab in breast cancer are still missing. Since epigenetic modifications can contribute to an aberrant regulation of angiogenesis and treatment resistance, we investigated the influence of DNA methylation patterns on bevacizumab efficacy. Methods: Genome-wide methylation profiling using the Illumina Infinium HumanMethylation450 BeadChip was performed in archival FFPE specimens of 36 patients with HER2-negative metastatic breast cancer treated with chemotherapy in combination with bevacizumab as first-line therapy ( learning set )...
2018: Theranostics
https://www.readbyqxmd.com/read/29719832/microenvironment-induced-non-sporadic-expression-of-the-axl-and-ckit-receptors-are-related-to-epithelial-plasticity-and-drug-resistance
#17
Tiina A Jokela, Agnete S T Engelsen, Agata Rybicka, Fanny A Pelissier Vatter, James C Garbe, Masaru Miyano, Crina Tiron, Dan Ferariu, Lars A Akslen, Martha R Stampfer, James B Lorens, Mark A LaBarge
The existence of rare cancer cells that sporadically acquire drug-tolerance through epigenetic mechanisms is proposed as one mechanism that drives cancer therapy failure. Here we provide evidence that specific microenvironments impose non-sporadic expression of proteins related to epithelial plasticity and drug resistance. Microarrays of robotically printed combinatorial microenvironments of known composition were used to make cell-based functional associations between microenvironments, which were design-inspired by normal and tumor-burdened breast tissues, and cell phenotypes...
2018: Frontiers in Cell and Developmental Biology
https://www.readbyqxmd.com/read/29714144/epigenetics-in-metastatic-breast-cancer-its-regulation-and-implications-in-diagnosis-prognosis-and-therapeutics
#18
Yuan Seng Wu, Zhong Yang Lee, Lay-Hong Chuah, Chun Wai Mai, Siew Ching Ngai
Despite advances in the treatment regimen, the high incidence rate of breast cancer (BC) deaths is mostly caused by metastasis. Recently, the aberrant epigenetic modifications, which involve DNA methylation, histone modifications and microRNA (miRNA) regulations become attractive targets to treat metastatic breast cancer (MBC). In this review, the epigenetic alterations of DNA methylation, histone modifications and miRNA regulations in regulating MBC is discussed. The preclinical and clinical trials of epigenetic drugs such as the inhibitor of DNA methyltransferase (DNMTi) and the inhibitor of histone deacetylase (HDACi), as a single or combined regimen with other epigenetic drug or standard chemotherapy drug to treat MBCs are discussed...
April 30, 2018: Current Cancer Drug Targets
https://www.readbyqxmd.com/read/29713632/antimetabolic-effects-of-polyphenols-in-breast-cancer-cells-focus-on-glucose-uptake-and-metabolism
#19
REVIEW
Elisa Keating, Fátima Martel
In the last years, metabolic reprogramming became a new key hallmark of tumor cells. One of its components is a deviant energetic metabolism, known as Warburg effect-an aerobic lactatogenesis- characterized by elevated rates of glucose uptake and consumption with high-lactate production even in the presence of oxygen. Because many cancer cells display a greater sensitivity to glucose deprivation-induced cytotoxicity than normal cells, inhibitors of glucose cellular uptake (facilitative glucose transporter 1 inhibitors) and oxidative metabolism (glycolysis inhibitors) are potential therapeutic targets in cancer treatment...
2018: Frontiers in Nutrition
https://www.readbyqxmd.com/read/29713043/epigenome-wide-association-study-of-adiposity-and-future-risk-of-obesity-related-diseases
#20
Gianluca Campanella, Marc J Gunter, Silvia Polidoro, Vittorio Krogh, Domenico Palli, Salvatore Panico, Carlotta Sacerdote, Rosario Tumino, Giovanni Fiorito, Simonetta Guarrera, Licia Iacoviello, Ingvar A Bergdahl, Beatrice Melin, Per Lenner, Theo M C M de Kok, Panagiotis Georgiadis, Jos C S Kleinjans, Soterios A Kyrtopoulos, H Bas Bueno-de-Mesquita, Karen A Lillycrop, Anne M May, N Charlotte Onland-Moret, Robert Murray, Elio Riboli, Monique Verschuren, Eiliv Lund, Nicolle Mode, Torkjel M Sandanger, Valentina Fiano, Morena Trevisan, Giuseppe Matullo, Philippe Froguel, Paul Elliott, Paolo Vineis, Marc Chadeau-Hyam
BACKGROUND: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction. METHODS: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework...
May 1, 2018: International Journal of Obesity: Journal of the International Association for the Study of Obesity
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