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https://www.readbyqxmd.com/read/28524162/targeted-sequencing-based-analyses-of-candidate-gene-variants-in-ulcerative-colitis-associated-colorectal-neoplasia
#1
Sanjiban Chakrabarty, Vinay Koshy Varghese, Pranoy Sahu, Pradyumna Jayaram, Bhadravathi M Shivakumar, Cannanore Ganesh Pai, Kapaettu Satyamoorthy
BACKGROUND: Long-standing ulcerative colitis (UC) leading to colorectal cancer (CRC) is one of the most serious and life-threatening consequences acknowledged globally. Ulcerative colitis-associated colorectal carcinogenesis showed distinct molecular alterations when compared with sporadic colorectal carcinoma. METHODS: Targeted sequencing of 409 genes in tissue samples of 18 long-standing UC subjects at high risk of colorectal carcinoma (UCHR) was performed to identify somatic driver mutations, which may be involved in the molecular changes during the transformation of non-dysplastic mucosa to high-grade dysplasia...
May 18, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28523964/epigenetics-in-endometrial-carcinogenesis-part-2-histone-modifications-chromatin-remodeling-and-noncoding-rnas
#2
Carla Bartosch, José Manuel Lopes, Carmen Jerónimo
Carcinogenesis is a multistep multifactorial process that involves the accumulation of genetic and epigenetic alterations. In the past two decades, there has been an exponential growth of knowledge establishing the importance of epigenetic changes in cancer. Our work focused on reviewing the main role of epigenetics in the pathogenesis of endometrial carcinoma, highlighting the reported results concerning each epigenetic mechanistic layer. In a previous review, we assessed DNA methylation alterations. The present review examines the contribution of histone modifications, chromatin remodeling and noncoding RNA alterations for endometrial carcinogenesis...
May 19, 2017: Epigenomics
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#3
Shama Prasada Kabekkodu, Sanjiban Chakrabarty, Supriti Ghosh, Angela Brand, Kapaettu Satyamoorthy
Epigenomics encompasses the study of genome-wide changes in DNA methylation, histone modifications and noncoding RNAs leading to altered transcription, chromatin structure, and posttranscription RNA processing, respectively, resulting in an altered rate of gene expression. The role of epigenetic modifications facilitating human diseases is well established. Previous studies have identified histone and cytosine code during normal and pathological conditions with special emphasis on how these modifications regulate transcriptional events...
May 19, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28499349/epimetheus-a-multi-profile-normalizer-for-epigenomic-sequencing-data
#4
Mohamed-Ashick M Saleem, Marco-Antonio Mendoza-Parra, Pierre-Etienne Cholley, Matthias Blum, Hinrich Gronemeyer
BACKGROUND: Exponentially increasing numbers of NGS-based epigenomic datasets in public repositories like GEO constitute an enormous source of information that is invaluable for integrative and comparative studies of gene regulatory mechanisms. One of today's challenges for such studies is to identify functionally informative local and global patterns of chromatin states in order to describe the regulatory impact of the epigenome in normal cell physiology and in case of pathological aberrations...
May 12, 2017: BMC Bioinformatics
https://www.readbyqxmd.com/read/28496053/chemical-and-structural-biology-of-protein-lysine-deacetylases
#5
Minoru Yoshida, Norio Kudo, Saori Kosono, Akihiro Ito
Histone acetylation is a reversible posttranslational modification that plays a fundamental role in regulating eukaryotic gene expression and chromatin structure/function. Key enzymes for removing acetyl groups from histones are metal (zinc)-dependent and NAD(+)-dependent histone deacetylases (HDACs). The molecular function of HDACs have been extensively characterized by various approaches including chemical, molecular, and structural biology, which demonstrated that HDACs regulate cell proliferation, differentiation, and metabolic homeostasis, and that their alterations are deeply involved in various human disorders including cancer...
2017: Proceedings of the Japan Academy. Series B, Physical and Biological Sciences
https://www.readbyqxmd.com/read/28485572/citrullination-methylation-crosstalk-on-histone-h3-regulates-er-target-gene-transcription
#6
Kathleen W Clancy, Anna-Maria Russell, Venkataraman Subramanian, Hannah Nguyen, Yuewei Qian, Robert M Campbell, Paul R Thompson
Posttranslational modifications of histone tails are a key contributor to epigenetic regulation. Histone H3 Arg26 and Lys27 are both modified by multiple enzymes, and their modifications have profound effects on gene expression. Citrullination of H3R26 by PAD2 and methylation of H3K27 by PRC2 have opposing downstream impacts on gene regulation; H3R26 citrullination activates gene expression, and H3K27 methylation represses gene expression. Both of these modifications are drivers of a variety of cancers, and their writer enzymes, PAD2 and EZH2, are the targets of drug therapies...
May 9, 2017: ACS Chemical Biology
https://www.readbyqxmd.com/read/28460463/set-oncoprotein-accumulation-regulates-transcription-through-dna-demethylation-and-histone-hypoacetylation
#7
Luciana O Almeida, Marinaldo P C Neto, Lucas O Sousa, Maryna A Tannous, Carlos Curti, Andreia M Leopoldino
Epigenetic modifications are essential in the control of normal cellular processes and cancer development. DNA methylation and histone acetylation are major epigenetic modifications involved in gene transcription and abnormal events driving the oncogenic process. SET protein accumulates in many cancer types, including head and neck squamous cell carcinoma (HNSCC); SET is a member of the INHAT complex that inhibits gene transcription associating with histones and preventing their acetylation. We explored how SET protein accumulation impacts on the regulation of gene expression, focusing on DNA methylation and histone acetylation...
April 18, 2017: Oncotarget
https://www.readbyqxmd.com/read/28454212/reciprocal-regulation-between-micrornas-and-epigenetic-machinery-in-colorectal-cancer
#8
Feng Wang, Yanlei Ma, Huamin Wang, Huanlong Qin
Epigenetics encompasses changes in DNA methylation, histone and chromatin structure, and non-coding RNAs, specifically microRNA (miRNA) expression. Recent advances in the rapidly evolving field of colorectal cancer (CRC) epigenetics have revealed a complicated network of reciprocal interconnections between miRNAs and other epigenetic machinery. On the one hand, miRNA expression may be regulated by epigenetic mechanisms including DNA methylation and histone modifications. However, miRNAs may affect the epigenetic machinery by directly targeting its enzymatic components...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445736/systematic-epigenomic-analysis-reveals-chromatin-states-associated-with-melanoma-progression
#9
Petko Fiziev, Kadir C Akdemir, John P Miller, Emily Z Keung, Neha S Samant, Sneha Sharma, Christopher A Natale, Christopher J Terranova, Mayinuer Maitituoheti, Samirkumar B Amin, Emmanuel Martinez-Ledesma, Mayura Dhamdhere, Jacob B Axelrad, Amiksha Shah, Christine S Cheng, Harshad Mahadeshwar, Sahil Seth, Michelle C Barton, Alexei Protopopov, Kenneth Y Tsai, Michael A Davies, Benjamin A Garcia, Ido Amit, Lynda Chin, Jason Ernst, Kunal Rai
The extent and nature of epigenomic changes associated with melanoma progression is poorly understood. Through systematic epigenomic profiling of 35 epigenetic modifications and transcriptomic analysis, we define chromatin state changes associated with melanomagenesis by using a cell phenotypic model of non-tumorigenic and tumorigenic states. Computation of specific chromatin state transitions showed loss of histone acetylations and H3K4me2/3 on regulatory regions proximal to specific cancer-regulatory genes in important melanoma-driving cell signaling pathways...
April 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28441146/epigenetic-regulation-of-glucose-metabolism
#10
Sapna Sharma, Jennifer Kriebel, Harald Grallert
PURPOSE OF REVIEW: Glucose metabolism is a central process in mammalian energy homeostasis. Its deregulation is a key factor in development of metabolic disease like diabetes and cancer. In recent decades, our understanding of gene regulation at the signaling, chromatin and posttranscriptional levels has seen dramatic developments. RECENT FINDINGS: A number of epigenetic mechanisms that do not affect the genetic code can be assessed with new technologies. However, increasing complexity becomes a major challenge for translation into clinical application...
April 24, 2017: Current Opinion in Clinical Nutrition and Metabolic Care
https://www.readbyqxmd.com/read/28432260/dual-histone-reader-zmynd8-inhibits-cancer-cell-invasion-by-positively-regulating-epithelial-genes
#11
Moitri Basu, Isha Sengupta, Wasim Khan, Dushyant Kumar Srivastava, Partha Chakrabarti, Siddhartha Roy, Chandrima Das
Enhanced migratory potential and invasiveness of cancer cells attribute crucially.in cancer progression. These phenotypes are achieved by precise alteration of invasion-associated genes through local epigenetic modifications which are recognized by a class of proteins termed as chromatin reader. ZMYND8 (zinc finger MYND (Myeloid, Nervy and DEAF-1)-type containing 8), a key component of transcription regulatory network, has been recently shown to be a novel reader of H3.1K36Me2/H4K16Ac marks. Through differential gene expression analysis upon silencing this chromatin reader, we identified a subset of genes involved in cell proliferation and invasion/migration regulated by ZMYND8...
April 21, 2017: Biochemical Journal
https://www.readbyqxmd.com/read/28412585/the-promise-of-epigenetic-therapy-reprogramming-the-cancer-epigenome
#12
REVIEW
Andrew D Kelly, Jean-Pierre J Issa
Epigenetics refers to heritable molecular determinants of phenotype independent of DNA sequence. Epigenetic features include DNA methylation, histone modifications, non-coding RNAs, and chromatin structure. The epigenetic status of cells plays a crucial role in determining their differentiation state and proper function within multicellular organisms. Disruption of these processes is now understood to be a major contributor to cancer development and progression, and recent efforts have attempted to pharmacologically reverse such altered epigenetics...
April 13, 2017: Current Opinion in Genetics & Development
https://www.readbyqxmd.com/read/28404599/molecular-pathways-metabolic-control-of-histone-methylation-and-gene-expression-in-cancer
#13
Thai Q Tran, Xazmin H Lowman, Mei Kong
Epigenetic alterations contribute to tumor development, progression, and therapeutic response. Many epigenetic enzymes use metabolic intermediates as cofactors to modify chromatin structure. Emerging evidence suggests that fluctuation in metabolite levels may regulate activities of these chromatin-modifying enzymes. Here we summarize recent progress in understanding the crosstalk between metabolism and epigenetic control of gene expression in cancer. We focus on how metabolic changes, due to diet, genetic mutations, or tumor microenvironment, regulate histone methylation status and consequently affect gene expression profiles to promote tumorigenesis...
April 12, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28401148/new-insights-into-the-epigenetics-of-hepatocellular-carcinoma
#14
REVIEW
Braira Wahid, Amjad Ali, Shazia Rafique, Muhammad Idrees
Hepatocellular Carcinoma (HCC) is one of the most predominant malignancies with high fatality rate. This deadly cancer is rising at an alarming rate because it is quite resistant to radio- and chemotherapy. Different epigenetic mechanisms such as histone modifications, DNA methylation, chromatin remodeling, and expression of noncoding RNAs drive the cell proliferation, invasion, metastasis, initiation, progression, and development of HCC. These epigenetic alterations because of potential reversibility open way towards the development of biomarkers and therapeutics...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28401060/therapeutic-targeting-of-histone-modifications-in-adult-and-pediatric-high-grade-glioma
#15
REVIEW
Maria J Williams, Will G B Singleton, Stephen P Lowis, Karim Malik, Kathreena M Kurian
Recent exciting work partly through The Cancer Genome Atlas has implicated epigenetic mechanisms including histone modifications in the development of both pediatric and adult high-grade glioma (HGG). Histone lysine methylation has emerged as an important player in regulating gene expression and chromatin function. Lysine (K) 27 (K27) is a critical residue in all seven histone 3 variants and the subject of posttranslational histone modifications, as it can be both methylated and acetylated. In pediatric HGG, two critical single-point mutations occur in the H3F3A gene encoding the regulatory histone variant H3...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28390392/emerging-role-of-mutations-in-epigenetic-regulators-including-mll2-derived-from-the-cancer-genome-atlas-for-cervical-cancer
#16
Xia Li
BACKGROUND: Cervical cancer is the second most common cause of cancer deaths in women worldwide. The aim of this study is to exploit novel pathogenic genes in cervical carcinogenesis. METHOD: The somatic mutations from 194 patients with cervical cancer were obtained from the Cancer Genome Atlas (TCGA) publically accessible exome-sequencing database. We investigated mutated gene enrichment in the 12 cancer core pathways and predicted possible post-translational modifications...
April 8, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28369194/crosstalk-between-epigenetics-and-metabolism-yin-and-yang-of-histone-demethylases-and-methyltransferases-in-cancer
#17
Fabian V Filipp
Histone methylation is an epigenetic modification of chromatin undergoing dynamic changes and balancing tissue-specific demands of proliferation and differentiation. In cancer, aberrant histone methylation can facilitate oncogenic and tumor suppression programs by modulating gene expression. Histone remodelers such as lysine methyltransferases and lysine demethylases are seemingly opposite or contrary forces but may be part of an interconnected network complementing each other. We identify several layers of molecular communication where epigenetic master regulators engage in crosstalk between tumor metabolism and histone remodeling...
March 24, 2017: Briefings in Functional Genomics
https://www.readbyqxmd.com/read/28356894/a-novel-epi-drug-therapy-based-on-the-suppression-of-bet-family-epigenetic-readers
#18
REVIEW
Dong-Guk Shin, Dashzeveg Bayarsaihan
Recent progress in epigenetic research has made a profound influence on pharmacoepigenomics, one of the fastest growing disciplines promising to provide new epi-drugs for the treatment of a broad range of diseases. Histone acetylation is among the most essential chromatin modifications underlying the dynamics of transcriptional activation. The acetylated genomic regions recruit the BET (bromodomain and extra-terminal) family of bromodomains (BRDs), thereby serving as a molecular scaffold in establishing RNA polymerase II specificity...
March 2017: Yale Journal of Biology and Medicine
https://www.readbyqxmd.com/read/28356029/oncogenic-role-of-set-i2pp2a-for-gynecologic-cancers
#19
Shi-Wen Jiang, Siliang Xu, Haibin Chen, Jiayin Liu, Ping Duan
SET (SE translocation, SET) is an evolutionarily conserved gene broadly expressed in various human tissues, especially in the gonadal and neural system. As a multitasking protein, SET is involved in essential cell processes such as histone modification, chromatin remodeling, DNA repair, gene transcription, and androgen synthesis. Recent studies showed that SET is overexpressed in breast cancers, ovary cancers and a variety of other malignancies. The strong correlation between SET expression levels and survival of ovarian cancer patients, and SET-mediated activation of androgen synthesis, strongly indicated that this factor may play a significant role in gynecologic cancers...
March 28, 2017: Current Drug Targets
https://www.readbyqxmd.com/read/28336670/pi3k-pathway-regulates-er-dependent-transcription-in-breast-cancer-through-the-epigenetic-regulator-kmt2d
#20
Eneda Toska, Hatice U Osmanbeyoglu, Pau Castel, Carmen Chan, Ronald C Hendrickson, Moshe Elkabets, Maura N Dickler, Maurizio Scaltriti, Christina S Leslie, Scott A Armstrong, José Baselga
Activating mutations in PIK3CA, the gene encoding phosphoinositide-(3)-kinase α (PI3Kα), are frequently found in estrogen receptor (ER)-positive breast cancer. PI3Kα inhibitors, now in late-stage clinical development, elicit a robust compensatory increase in ER-dependent transcription that limits therapeutic efficacy. We investigated the chromatin-based mechanisms leading to the activation of ER upon PI3Kα inhibition. We found that PI3Kα inhibition mediates an open chromatin state at the ER target loci in breast cancer models and clinical samples...
March 24, 2017: Science
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