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histone modification chromatin cancer

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https://www.readbyqxmd.com/read/29777275/overexpression-of-abcb4-contributes-to-acquired-doxorubicin-resistance-in-breast-cancer-cells-in-vitro
#1
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/29773832/distinct-epigenetic-landscapes-underlie-the-pathobiology-of-pancreatic-cancer-subtypes
#2
Gwen Lomberk, Yuna Blum, Rémy Nicolle, Asha Nair, Krutika Satish Gaonkar, Laetitia Marisa, Angela Mathison, Zhifu Sun, Huihuang Yan, Nabila Elarouci, Lucile Armenoult, Mira Ayadi, Tamas Ordog, Jeong-Heon Lee, Gavin Oliver, Eric Klee, Vincent Moutardier, Odile Gayet, Benjamin Bian, Pauline Duconseil, Marine Gilabert, Martin Bigonnet, Stephane Garcia, Olivier Turrini, Jean-Robert Delpero, Marc Giovannini, Philippe Grandval, Mohamed Gasmi, Veronique Secq, Aurélien De Reyniès, Nelson Dusetti, Juan Iovanna, Raul Urrutia
Recent studies have offered ample insight into genome-wide expression patterns to define pancreatic ductal adenocarcinoma (PDAC) subtypes, although there remains a lack of knowledge regarding the underlying epigenomics of PDAC. Here we perform multi-parametric integrative analyses of chromatin immunoprecipitation-sequencing (ChIP-seq) on multiple histone modifications, RNA-sequencing (RNA-seq), and DNA methylation to define epigenomic landscapes for PDAC subtypes, which can predict their relative aggressiveness and survival...
May 17, 2018: Nature Communications
https://www.readbyqxmd.com/read/29769529/methionine-metabolism-influences-genomic-architecture-and-gene-expression-through-h3k4me3-peak-width
#3
Ziwei Dai, Samantha J Mentch, Xia Gao, Sailendra N Nichenametla, Jason W Locasale
Nutrition and metabolism are known to influence chromatin biology and epigenetics through post-translational modifications, yet how this interaction influences genomic architecture and connects to gene expression is unknown. Here we consider, as a model, the metabolically-driven dynamics of H3K4me3, a histone methylation mark that is known to encode information about active transcription, cell identity, and tumor suppression. We analyze the genome-wide changes in H3K4me3 and gene expression in response to alterations in methionine availability in both normal mouse physiology and human cancer cells...
May 16, 2018: Nature Communications
https://www.readbyqxmd.com/read/29763912/-a-succinate-ether-derivative-of-tocotrienol-enhances-dickkopf-1-gene-expression-through-epigenetic-alterations-in-malignant-mesothelioma-cells
#4
Ayami Sato, Haruka Ueno, Momoka Fusegi, Saki Kaneko, Kakeru Kohno, Nantiga Virgona, Akira Ando, Yuko Sekine, Tomohiro Yano
BACKGROUND: Wnt signaling plays an essential role in tumor cell growth, including the development of malignant mesothelioma (MM). Epigenetic silencing of negative Wnt regulators leading to constitutive Wnt signaling has been observed in various cancers and warrants further attention. We have reported that a succinate ether derivative of α-tocotrienol (T3E) has potent cytotoxic effects in MM cells. Thus, in this study, we investigated whether the anti-MM effect of T3E could be mediated via the epigenetic alteration of the Wnt antagonist gene, Dickkopf-1 (DKK1)...
May 15, 2018: Pharmacology
https://www.readbyqxmd.com/read/29759441/nuclear-organization-mediates-cancer-compromised-genetic-and-epigenetic-control
#5
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/29755673/role-of-epigenetic-factors-in-the-selection-of-the-alternative-splicing-isoforms-of-human-kras-in-colorectal-cancer-cell-lines
#6
Ángela L Riffo-Campos, Francisco Gimeno-Valiente, Fernanda M Rodríguez, Andrés Cervantes, Gerardo López-Rodas, Luis Franco, Josefa Castillo
Mutation-driven activation of KRAS is crucial to cancer development. The human gene yields four mRNA splicing isoforms, 4A and 4B being translated to protein. Their different properties and oncogenic potential have been studied, but the mechanisms deciding the ratio 4A/4B are not known. To address this issue, the expression of the four KRAS isoforms was determined in 9 human colorectal cancer cell lines. HCT116 and SW48 were further selected because they present the highest difference in the ratio 4A/4B (twice as much in HCT116 than in SW48)...
April 17, 2018: Oncotarget
https://www.readbyqxmd.com/read/29752422/a-histone-reader-becomes-the-readout
#7
Catherine A Musselman, Tatiana G Kutateladze
Chromatin signaling events are critical for the dynamic regulation of the genome. Although much has been learned about histone modification in these events, the modification of nonhistone chromatin regulators and cross-talk between these pathways is less well understood. Here, Appikonda et al. demonstrate that the transcription co-factor and oncoprotein TRIM24 (tripartite motif-containing protein 24) is SUMOylated upon association with a specific histone modification signature, which regulates the transcription of genes involved in cell adhesion...
May 11, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29749437/oncogenic-il7r-is-downregulated-by-histone-deacetylase-inhibitor-in-esophageal-squamous-cell-carcinoma-via-modulation-of-acetylated-foxo1
#8
Myoung Jun Kim, Sung Kyung Choi, Seong Hwi Hong, Jung Woo Eun, Suk Woo Nam, Jeung-Whan Han, Jueng Soo You
The interleukin-7 receptor (IL7R) is generally expressed in immune cells and is critical in survival, development and homeostasis in the immune system. Advanced genome-wide cancer studies have reported that IL7R is genetically amplified in human esophageal squamous cell carcinoma (ESCC), however, the exact role of IL7R in ESCC has not been investigated. In the present study, it was found that IL7R was overexpressed in ESCC cohorts and the loss of IL7R induced anti-oncogenic effects in ESCC cell lines. A small panel of epigenetic drugs were screened for their ability to downregulate the expression of IL7R...
May 2, 2018: International Journal of Oncology
https://www.readbyqxmd.com/read/29736013/utx-mediated-enhancer-and-chromatin-remodeling-suppresses-myeloid-leukemogenesis-through-noncatalytic-inverse-regulation-of-ets-and-gata-programs
#9
Malgorzata Gozdecka, Eshwar Meduri, Milena Mazan, Konstantinos Tzelepis, Monika Dudek, Andrew J Knights, Mercedes Pardo, Lu Yu, Jyoti S Choudhary, Emmanouil Metzakopian, Vivek Iyer, Haiyang Yun, Naomi Park, Ignacio Varela, Ruben Bautista, Grace Collord, Oliver Dovey, Dimitrios A Garyfallos, Etienne De Braekeleer, Saki Kondo, Jonathan Cooper, Berthold Göttgens, Lars Bullinger, Paul A Northcott, David Adams, George S Vassiliou, Brian J P Huntly
The histone H3 Lys27-specific demethylase UTX (or KDM6A) is targeted by loss-of-function mutations in multiple cancers. Here, we demonstrate that UTX suppresses myeloid leukemogenesis through noncatalytic functions, a property shared with its catalytically inactive Y-chromosome paralog, UTY (or KDM6C). In keeping with this, we demonstrate concomitant loss/mutation of KDM6A (UTX) and UTY in multiple human cancers. Mechanistically, global genomic profiling showed only minor changes in H3K27me3 but significant and bidirectional alterations in H3K27ac and chromatin accessibility; a predominant loss of H3K4me1 modifications; alterations in ETS and GATA-factor binding; and altered gene expression after Utx loss...
May 7, 2018: Nature Genetics
https://www.readbyqxmd.com/read/29721215/epigenetic-regulation-of-long-non-coding-rnas-in-gastric-cancer
#10
REVIEW
Zhixia Zhou, Zhijuan Lin, Xin Pang, Muhammad Akram Tariq, Xiang Ao, Peifeng Li, Jianxun Wang
Gastric cancer is one of the most common cancers and is the second leading cause of cancer mortality worldwide. Therefore, it is urgent to explore new molecular biomarkers for early diagnosis, early treatment and prognosis for gastric cancer patients. Recently, increasing evidence has shown that epigenetic changes, such as aberrant DNA methylation, histone modifications, and noncoding RNAs (ncRNAs) expression, play substantial roles in the development and progression of malignancies. Among these changes, long non-coding RNAs (lncRNAs), a novel class of ncRNAs, are emerging as highly versatile actors in a variety of cellular processes by regulating gene expression at the epigenetic level as well as at the transcriptional and post-transcriptional levels...
April 10, 2018: Oncotarget
https://www.readbyqxmd.com/read/29700278/targeting-of-epigenetic-regulators-in-neuroblastoma
#11
REVIEW
Luz Jubierre, Carlos Jiménez, Eric Rovira, Aroa Soriano, Constantino Sábado, Luis Gros, Anna Llort, Raquel Hladun, Josep Roma, Josep Sánchez de Toledo, Soledad Gallego, Miguel F Segura
Approximately 15,000 new cases of pediatric cancer are diagnosed yearly in Europe, with 8-10% corresponding to neuroblastoma, a rare disease with an incidence of 8-9 cases per million children <15 years of age. Although the survival rate for low-risk and intermediate-risk patients is excellent, half of children with high-risk, refractory, or relapsed tumors will be cured, and two-thirds of the other half will suffer major side effects and life-long disabilities. Epigenetic therapies aimed at reversing the oncogenic alterations in chromatin structure and function are an emerging alternative against aggressive tumors that are or will become resistant to conventional treatments...
April 27, 2018: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/29683440/an-integrated-platform-for-genome-wide-mapping-of-chromatin-states-using-high-throughput-chip-sequencing-in-tumor-tissues
#12
Christopher Terranova, Ming Tang, Elias Orouji, Mayinuer Maitituoheti, Ayush Raman, Samirkumar Amin, Zhiyi Liu, Kunal Rai
Histone modifications constitute a major component of the epigenome and play important regulatory roles in determining the transcriptional status of associated loci. In addition, the presence of specific modifications has been used to determine the position and identity non-coding functional elements such as enhancers. In recent years, chromatin immunoprecipitation followed by next generation sequencing (ChIP-seq) has become a powerful tool in determining the genome-wide profiles of individual histone modifications...
April 5, 2018: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29680858/relationship-between-histone-deacetylase-3-hdac3-and-breast-cancer
#13
Zhuhong Cui, Mingjun Xie, Zhenru Wu, Yujun Shi
BACKGROUND The modification of histone acetylation and deacetylation is the most important mechanism of chromatin remodeling. These modifications are a subset of epigenetic alterations which affect tumorigenesis and progression through changes in gene expression and cell growth. Results of histone modification studies prompted us to explore the therapeutic and prognostic significance of histone deacetylase 3 (HDAC3) expression in patients with breast cancer. MATERIAL AND METHODS Immunohistochemical (IHC) staining was used to detect HDAC3 expression in a tissue microarray (TMA) that included 145 patients diagnosed with invasive ductal breast carcinoma...
April 22, 2018: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/29679095/implication-of-the-vrk1-chromatin-kinase-in-the-signaling-responses-to-dna-damage-a-therapeutic-target
#14
REVIEW
Ignacio Campillo-Marcos, Pedro A Lazo
DNA damage causes a local distortion of chromatin that triggers the sequential processes that participate in specific DNA repair mechanisms. This initiation of the repair response requires the involvement of a protein whose activity can be regulated by histones. Kinases are candidates to regulate and coordinate the connection between a locally altered chromatin and the response initiating signals that lead to identification of the type of lesion and the sequential steps required in specific DNA damage responses (DDR)...
April 20, 2018: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/29667342/middle-down-characterization-of-the-cell-cycle-dependence-of-histone-h4-post-translational-modifications-and-proteoforms
#15
Tingting Jiang, Michael E Hoover, Matthew V Holt, Michael A Freitas, Alan G Marshall, Nicolas L Young
Post-translational modifications (PTMs) of histones are important epigenetic regulatory mechanisms that are often dysregulated in cancer. We employ middle-down proteomics to investigate the PTMs and proteoforms of histone H4 during cell cycle progression. We use pH gradient weak cation exchange-hydrophilic interaction liquid chromatography (WCX-HILIC) for on-line liquid chromatography-mass spectrometry analysis to separate and analyze the proteoforms of histone H4. This provides enhanced separation of proteoforms, including positional isomers, and simplifies downstream data analysis...
April 17, 2018: Proteomics
https://www.readbyqxmd.com/read/29665865/integrative-analysis-reveals-functional-and-regulatory-roles-of-h3k79me2-in-mediating-alternative-splicing
#16
Tianbao Li, Qi Liu, Nick Garza, Steven Kornblau, Victor X Jin
BACKGROUND: Accumulating evidence suggests alternative splicing (AS) is a co-transcriptional splicing process not only controlled by RNA-binding splicing factors, but also mediated by epigenetic regulators, such as chromatin structure, nucleosome density, and histone modification. Aberrant AS plays an important role in regulating various diseases, including cancers. METHODS: In this study, we integrated AS events derived from RNA-seq with H3K79me2 ChIP-seq data across 34 different normal and cancer cell types and found the higher enrichment of H3K79me2 in two AS types, skipping exon (SE) and alternative 3' splice site (A3SS)...
April 17, 2018: Genome Medicine
https://www.readbyqxmd.com/read/29659013/dietary-fat-and-fiber-interact-to-uniquely-modify-global-histone-post-translational-epigenetic-programming-in-a-rat-colon-cancer-progression-model
#17
Karen Triff, Mathew W McLean, Evelyn Callaway, Jennifer Goldsby, Ivan Ivanov, Robert S Chapkin
Dietary fermentable fiber generates short-chain fatty acids (SCFA), e.g., butyrate, in the colonic lumen which serves as a chemoprotective histone deacetylase inhibitor and/or as an acetylation substrate for histone acetylases. In addition, n-3 polyunsaturated fatty acids (n-3 PUFA) in fish oil can affect the chromatin landscape by acting as ligands for tumor suppressive nuclear receptors. In an effort to gain insight into the global dimension of post-translational modification of histones (including H3K4me3 and H3K9ac) and clarify the chemoprotective impact of dietary bioactive compounds on transcriptional control in a preclinical model of colon cancer, we generated high-resolution genome-wide RNA (RNA-Seq) and "chromatin-state" (H3K4me3-seq and H3K9ac-seq) maps for intestinal (epithelial colonocytes) crypts in rats treated with a colon carcinogen and fed diets containing bioactive (i) fish oil, (ii) fermentable fiber (a rich source of SCFA), (iii) a combination of fish oil plus pectin or (iv) control, devoid of fish oil or pectin...
April 16, 2018: International Journal of Cancer. Journal International du Cancer
https://www.readbyqxmd.com/read/29569274/the-effects-of-acetaldehyde-exposure-on-histone-modifications-and-chromatin-structure-in-human-lung-bronchial-epithelial-cells
#18
Danqi Chen, Lei Fang, Hongjie Li, Chunyuan Jin
As the primary metabolite of alcohol and the most abundant carcinogen in tobacco smoke, acetaldehyde is linked to a number of human diseases associated with chronic alcohol consumption and smoking including cancers. In addition to direct DNA damage as a result of the formation of acetaldehyde-DNA adducts, acetaldehyde may also indirectly impact proper genome function through the formation of protein adducts. Histone proteins are the major component of the chromatin. Post-translational histone modifications (PTMs) are critically important for the maintenance of genetic and epigenetic stability...
March 22, 2018: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/29562725/genetic-and-epigenetic-regulation-in-nonalcoholic-fatty-liver-disease-nafld
#19
REVIEW
José A Del Campo, Rocío Gallego-Durán, Paloma Gallego, Lourdes Grande
Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology has allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3 , MBOAT7 ). On the other hand, epigenetic changes interact with inherited risk factors to determine an individual's susceptibility to NAFLD...
March 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29552712/epigenetic-mechanisms-and-events-in-gastric-cancer-emerging-novel-biomarkers
#20
REVIEW
Puneet, Hasan Raza Kazmi, Soni Kumari, Satendra Tiwari, A Khanna, Gopeshwar Narayan
Gastric cancer is one of the most common malignancy worldwide. The various genetic and epigenetic events have been found to be associated with its carcinogenesis. The epigenetic is a heritable and transient/reversible change in the gene expression that is not accompanied by modification in the DNA sequence. This event is characterized by the alteration in the promoter CpG island of the gene or histone modification. These events are associated with silencing of critical tumor suppressor gene and activation of oncogenes leading to carcinogenesis...
March 19, 2018: Pathology Oncology Research: POR
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