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Epigenetics and cancer

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https://www.readbyqxmd.com/read/28822237/beyond-genomics-targeting-the-epigenome-in-diffuse-large-b-cell-lymphoma
#1
REVIEW
Andrea Kühnl, David Cunningham, Ian Chau
After decades of intense research on genetic alterations in cancer and successful implementation of genetically-based targeted therapies, the field of cancer epigenetics is only beginning to be fully recognized. The discovery of frequent mutations in genes modifying the epigenome in diffuse large B-cell lymphoma (DLBCL) has highlighted the outstanding role of epigenetic deregulation in this disease. Identification of epigenetically-driven DLBCL subgroups and development of novel epigenetic drugs have rapidly advanced...
August 9, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28820498/interference-of-apoptosis-by-hepatitis-b-virus
#2
REVIEW
Shaoli Lin, Yan-Jin Zhang
Hepatitis B virus (HBV) causes liver diseases that have been a consistent problem for human health, leading to more than one million deaths every year worldwide. A large proportion of hepatocellular carcinoma (HCC) cases across the world are closely associated with chronic HBV infection. Apoptosis is a programmed cell death and is frequently altered in cancer development. HBV infection interferes with the apoptosis signaling to promote HCC progression and viral proliferation. The HBV-mediated alteration of apoptosis is achieved via interference with cellular signaling pathways and regulation of epigenetics...
August 18, 2017: Viruses
https://www.readbyqxmd.com/read/28820292/p53-binding-sites-in-normal-and-cancer-cells-are-characterized-by-distinct-chromatin-context
#3
Feifei Bao, Peter R LoVerso, Jeffrey N Fisk, Victor B Zhurkin, Feng Cui
The tumor suppressor protein p53 interacts with DNA in a sequence-dependent manner. Thousands of p53 binding sites have been mapped genome-wide in normal and cancer cells. However, the way p53 selectively binds its cognate sites in different types of cells is not fully understood. Here, we performed a comprehensive analysis of 25 published p53 cistromes and identified 3,551 and 6,039 'high-confidence' binding sites in normal and cancer cells, respectively. Our analysis revealed two distinct epigenetic features underlying p53-DNA interactions in vivo...
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28820176/5-hydroxymethylcytosine-signatures-in-cell-free-dna-provide-information-about-tumor-types-and-stages
#4
Chun-Xiao Song, Senlin Yin, Li Ma, Amanda Wheeler, Yu Chen, Yan Zhang, Bin Liu, Junjie Xiong, Weihan Zhang, Jiankun Hu, Zongguang Zhou, Biao Dong, Zhiqi Tian, Stefanie S Jeffrey, Mei-Sze Chua, Samuel So, Weimin Li, Yuquan Wei, Jiajie Diao, Dan Xie, Stephen R Quake
5-Hydroxymethylcytosine (5hmC) is an important mammalian DNA epigenetic modification that has been linked to gene regulation and cancer pathogenesis. Here we explored the diagnostic potential of 5hmC in circulating cell-free DNA (cfDNA) using a sensitive chemical labeling-based low-input shotgun sequencing approach. We sequenced cell-free 5hmC from 49 patients of seven different cancer types and found distinct features that could be used to predict cancer types and stages with high accuracy. Specifically, we discovered that lung cancer leads to a progressive global loss of 5hmC in cfDNA, whereas hepatocellular carcinoma and pancreatic cancer lead to disease-specific changes in the cell-free hydroxymethylome...
August 18, 2017: Cell Research
https://www.readbyqxmd.com/read/28820062/urokinase-type-plasminogen-activator-and-the-molecular-mechanisms-of-its-regulation-in-cancer
#5
Juan Francisco Santibanez
Urokinase type plasminogen activator (uPA) is a 53-kDa serine protease initially synthesized as a catalytically inactive single chain polypeptide. Inactive-uPA is subject to proteolytic cleavage which results in the two-chain active protein. uPA plays key roles in the enhancement of cell malignancy during tumor progression. uPA is finely regulated in normal cells, but dysregulated in tumor cells, which results in increased cellular invasion capacities reflecting changes in uPA activity and expression during tumor progression...
August 18, 2017: Protein and Peptide Letters
https://www.readbyqxmd.com/read/28819251/g9a-regulates-breast-cancer-growth-by-modulating-iron-homeostasis-through-the-repression-of-ferroxidase-hephaestin
#6
Ya-Fang Wang, Jie Zhang, Yi Su, Yan-Yan Shen, Dong-Xian Jiang, Ying-Yong Hou, Mei-Yu Geng, Jian Ding, Yi Chen
G9a, a H3K9 methyltransferase, shows elevated expression in many types of human cancers, particularly breast cancer. However, the tumorigenic mechanism of G9a is still far from clear. Here we report that G9a exerts its oncogenic function in breast cancer by repressing hephaestin and destruction cellular iron homeostasis. In the case of pharmacological inhibition or short hairpin RNA interference-mediated suppression of G9a, the expression and activity of hephaestin increases, leading to the observed decrease of intracellular labile iron content and the disturbance of breast cancer cell growth in vitro and in vivo...
August 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28819152/dissecting-the-genomic-activity-of-a-transcriptional-regulator-by-the-integrative-analysis-of-omics-data
#7
Giulio Ferrero, Valentina Miano, Marco Beccuti, Gianfranco Balbo, Michele De Bortoli, Francesca Cordero
In the study of genomic regulation, strategies to integrate the data produced by Next Generation Sequencing (NGS)-based technologies in a meaningful ensemble are eagerly awaited and must continuously evolve. Here, we describe an integrative strategy for the analysis of data generated by chromatin immunoprecipitation followed by NGS which combines algorithms for data overlap, normalization and epigenetic state analysis. The performance of our strategy is illustrated by presenting the analysis of data relative to the transcriptional regulator Estrogen Receptor alpha (ERα) in MCF-7 breast cancer cells and of Glucocorticoid Receptor (GR) in A549 lung cancer cells...
August 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28818454/the-anti-tumor-effect-of-intravesical-administration-of-normal-urothelial-cells-on-bladder-cancer
#8
Chi-Ping Huang, Chi-Cheng Chen, Chih-Rong Shyr
BACKGROUND AIMS: Urothelial bladder cancer (UBC) is the second most common cancer of the genitourinary tract and for advanced forms of the disease it has a high mortality rate. There are no approved new molecularly targeted agents or chemotherapeutics for advanced UBC beyond cisplatin-based chemotherapy except the recently approved anti-programmed death ligand 1 (anti-PD-1/PD-L1) antibody. With complex genetic and epigenetic alterations in tumors, despite several druggable targets identified, to cure UBC is still a challenging unmet medical need...
August 14, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28816574/sgt1-hsp90-complex-is-required-for-cenp-a-deposition-at-centromeres
#9
Yohei Niikura, Risa Kitagawa, Hiroo Ogi, Katsumi Kitagawa
The centromere plays an essential role in accurate chromosome segregation, and defects in its function lead to aneuploidy and thus cancer. The centromere-specific histone H3 variant CENP-A is proposed to be the epigenetic mark of the centromere, as active centromeres require CENP-A-containing nucleosomes to direct the recruitment of multiple kinetochore proteins. CENP-A K124 ubiquitylation, mediated by CUL4A-RBX1-COPS8 E3 ligase activity, is required for CENP-A deposition at the centromere. However, the mechanism that controls the E3 ligase activity of the CUL4A-RBX1-COPS8 complex remains obscure...
August 17, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28816066/stressing-the-epi-genome-dealing-with-ros-in-cancer
#10
Akshay V Bhat, Shainan Hora, Ananya Pal, Sudhakar Jha, Reshma Taneja
SIGNIFICANCE: Growing evidence indicates cross-talk between Reactive oxygen species (ROS) and several key epigenetic processes like DNA methylation, histone modifications and miRNAs in normal physiology and human pathologies including cancer. This review focuses on how ROS-induced oxidative stress, metabolic intermediates and epigenetic processes influence each other in various cancers. Recent Advances: ROS alters chromatin structure and metabolism which impact the epigenetic landscape in cancer cells...
August 17, 2017: Antioxidants & Redox Signaling
https://www.readbyqxmd.com/read/28814981/cpg-location-and-methylation-level-are-crucial-factors-for-the-early-detection-of-oral-squamous-cell-carcinoma-in-brushing-samples-using-bisulfite-sequencing-of-a-13-gene-panel
#11
Luca Morandi, Davide Gissi, Achille Tarsitano, Sofia Asioli, Andrea Gabusi, Claudio Marchetti, Lucio Montebugnoli, Maria Pia Foschini
BACKGROUND: Oral squamous cell carcinoma (OSCC) is usually diagnosed at an advanced stage and is commonly preceded by oral premalignant lesions. The mortality rates have remained unchanged (50% within 5 years after diagnosis), and it is related to tobacco smoking and alcohol intake. Novel molecular markers for early diagnosis are urgently needed. The purpose of this study was to evaluate the diagnostic value of methylation level in a set of 18 genes by bisulfite next-generation sequencing...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28814673/human-lung-tumor-foxp-tregs-upregulate-four-treg-locking-transcription-factors
#12
Tatiana Akimova, Tianyi Zhang, Dmitri Negorev, Sunil Singhal, Jason Stadanlick, Abhishek Rao, Michael Annunziata, Matthew H Levine, Ulf H Beier, Joshua M Diamond, Jason D Christie, Steven M Albelda, Evgeniy B Eruslanov, Wayne W Hancock
Experimental data indicate that FOXP3+ Tregs can markedly curtail host antitumor immune responses, but the properties of human intratumoral Tregs are still largely unknown, in part due to significant methodologic problems. We studied the phenotypic, functional, epigenetic, and transcriptional features of Tregs in 92 patients with non-small-cell lung cancer, comparing the features of Tregs within tumors versus corresponding blood, lung, and lymph node samples. Intratumoral Treg numbers and suppressive function were significantly increased compared with all other sites but did not display a distinctive phenotype by flow cytometry...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28812986/epigenome-aberrations-emerging-driving-factors-of-the-clear-cell-renal-cell-carcinoma
#13
REVIEW
Ali Mehdi, Yasser Riazalhosseini
Clear cell renal cell carcinoma (ccRCC), the most common form of Kidney cancer, is characterized by frequent mutations of the von Hippel-Lindau (VHL) tumor suppressor gene in ~85% of sporadic cases. Loss of pVHL function affects multiple cellular processes, among which the activation of hypoxia inducible factor (HIF) pathway is the best-known function. Constitutive activation of HIF signaling in turn activates hundreds of genes involved in numerous oncogenic pathways, which contribute to the development or progression of ccRCC...
August 16, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28811977/epigenetic-regulation-of-the-extrinsic-oncosuppressor-ptx3-gene-in-inflammation-and-cancer
#14
Marcello Rubino, Paolo Kunderfranco, Gianluca Basso, Carolina Magdalen Greco, Fabio Pasqualini, Simone Serio, Massimo Roncalli, Luigi Laghi, Alberto Mantovani, Roberto Papait, Cecilia Garlanda
PTX3 is a component of the humoral arm of innate immunity and an extrinsic oncosuppressor gene taming tumor-promoting inflammation. Here, we show that two enhancers differently regulate PTX3 expression: enhancer 1, located 230 kb upstream of PTX3 promoter, mediated the action of inflammatory transcription factors; and enhancer 2, encompassing PTX3 second exon, was implicated in pre-initiation complex assembly. Polycomb repressive complex 2 silenced these regulatory elements and the promoter in basal condition...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28811844/lsd1-dual-function-in-mediating-epigenetic-corruption-of-the-vitamin-d-signaling-in-prostate-cancer
#15
Sebastiano Battaglia, Ellen Karasik, Bryan Gillard, Jennifer Williams, Trisha Winchester, Michael T Moser, Dominic J Smiraglia, Barbara A Foster
BACKGROUND: Lysine-specific demethylase 1A (LSD1) is a key regulator of the androgen (AR) and estrogen receptors (ER), and LSD1 levels correlate with tumor aggressiveness. Here, we demonstrate that LSD1 regulates vitamin D receptor (VDR) activity and is a mediator of 1,25(OH)2-D3 (vitamin D) action in prostate cancer (PCa). METHODS: Athymic nude mice were xenografted with CWR22 cells and monitored weekly after testosterone pellet removal. Expression of LSD1 and VDR (IHC) were correlated with tumor growth using log-rank test...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28809126/comprehensive-epigenetic-analysis-of-the-signature-genes-in-lung-adenocarcinoma
#16
Yunfeng Zhang, Weidong Zhao, Jia Zhang
AIM: This study aimed to explore the epigenetic modifications of signature genes in lung adenocarcinoma. MATERIALS & METHODS: The data of miRNA expression, mRNA expression and DNA methylation were downloaded from The Cancer Genome Atlas. Differential analysis was performed, followed by correlation analysis of miRNA-mRNA and DNA methylation-mRNA. RESULTS: A total of 14 significant inverse correlations between gene expression and DNA methylation were identified, the expressions of which were selected for further validation via GSE27262, displaying similar pattern with that of the integrated analysis...
August 15, 2017: Epigenomics
https://www.readbyqxmd.com/read/28807942/nuclear-fak-and-runx1-cooperate-to-regulate-igfbp3-cell-cycle-progression-and-tumor-growth
#17
Marta Canel, Adam Byron, Andrew H Sims, Jessy Cartier, Hitesh Patel, Margaret C Frame, Valerie G Brunton, Bryan Serrels, Alan Serrels
Nuclear focal adhesion kinase (FAK) is a potentially important regulator of gene expression in cancer, impacting both cellular function and the composition of the surrounding tumor microenvironment. Here we report in a murine model of skin squamous cell carcinoma (SCC) that nuclear FAK regulates Runx1-dependent transcription of insulin-like growth factor binding protein 3 (IGFBP3), and that this regulates SCC cell cycle progression and tumor growth in vivo. Furthermore, we identified a novel molecular complex between FAK and Runx1 in the nucleus of SCC cells and showed that FAK interacted with a number of Runx1 regulatory proteins, including Sin3a and other epigenetic modifiers known to alter Runx1 transcriptional function through post-translational modification...
August 14, 2017: Cancer Research
https://www.readbyqxmd.com/read/28807688/hypochlorous-acid-induced-structural-and-conformational-modifications-in-human-dna-a-multi-spectroscopic-study
#18
Irfan Qadir Tantry, Sana Waris, Safia Habib, Rizwan Hasan Khan, Riaz Mahmood, Asif Ali
Hypochlorous acid (HOCl) is generated by activated phagocytes at the site of inflammation. Exposure of DNA to HOCl results in base and nucleotide modifications causing DNA damage, which is one of the leading causes of various pathological conditions including carcinogenesis. In the present work, various biophysical techniques were used to study HOCl induced structural and conformational changes in human placental DNA. The HOCl modified DNA showed hyperchromicity, reduced fluorescence and decrease in melting temperature...
August 11, 2017: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/28807546/epigenetic-drivers-of-tumourigenesis-and-cancer-metastasis
#19
REVIEW
Aniruddha Chatterjee, Euan J Rodger, Michael R Eccles
Since the completion of the first human genome sequence and the advent of next generation sequencing technologies, remarkable progress has been made in understanding the genetic basis of cancer. These studies have mainly defined genetic changes as either causal, providing a selective advantage to the cancer cell (a driver mutation) or consequential with no selective advantage (not directly causal, a passenger mutation). A vast unresolved question is how a primary cancer cell becomes metastatic and what are the molecular events that underpin this process...
August 11, 2017: Seminars in Cancer Biology
https://www.readbyqxmd.com/read/28807232/ovarian-cancer-novel-molecular-aspects-for-clinical-assessment
#20
REVIEW
Raffaele Palmirotta, Erica Silvestris, Stella D'Oronzo, Angela Cardascia, Franco Silvestris
Ovarian cancer is a very heterogeneous tumor which has been traditionally characterized according to the different histological subtypes and differentiation degree. In recent years, innovative molecular screening biotechnologies have allowed to identify further subtypes of this cancer based on gene expression profiles, mutational features, and epigenetic factors. These novel classification systems emphasizing the molecular signatures within the broad spectrum of ovarian cancer have not only allowed a more precise prognostic prediction, but also proper therapeutic strategies for specific subgroups of patients...
September 2017: Critical Reviews in Oncology/hematology
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