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Cancer epigenetics

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https://www.readbyqxmd.com/read/28527406/the-relevance-of-ki-calculation-for-bi-substrate-enzymes-illustrated-by-kinetic-evaluation-of-a-novel-lysine-k-acetyltransferase-8-inhibitor
#1
Hannah Wapenaar, Thea van den Bosch, Niek G J Leus, Petra E van der Wouden, Nikolaos Eleftheriadis, Jos Hermans, Gebremedhin Solomon Hailu, Dante Rotili, Antonello Mai, Alexander Dömling, Rainer Bischoff, Hidde J Haisma, Frank J Dekker
Histone acetyltransferases (HATs) are important mediators of epigenetic post-translational modifications of histones that play important roles in health and disease. A disturbance of these modifications can result in disease states, such as cancer or inflammatory diseases. Inhibitors of HATs (HATi) such as lysine (K) acetyltransferase 8 (KAT8), could be used to study the epigenetic processes in diseases related to these enzymes or to investigate HATs as therapeutic targets. However, the development of HATi is challenged by the difficulties in kinetic characterization of HAT enzymes and their inhibitors to enable calculation of a reproducible inhibitory potency...
May 5, 2017: European Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/28526736/chd4-mediated-dna-hypermethylation-promotes-colorectal-cancer
#2
(no author information available yet)
CHD4 maintains epigenetic silencing of tumor suppressor genes to promote tumorigenesis.
May 19, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28526414/a-novel-sirt1-inhibitor-4bb-induces-apoptosis-in-hct116-human-colon-carcinoma-cells-partially-by-activating-p53
#3
Ananga Ghosh, Amrita Sengupta, Guru Pavan Kumar Seerapu, Ali Nakhi, E V Venkat Shivaji Ramarao, Navneet Bung, Gopalakrishnan Bulusu, Manojit Pal, Devyani Haldar
The NAD+-dependent protein deacetylase SIRT1 has emerged as an important target for epigenetic therapeutics of colon cancer as its increased expression is associated with cancer progression. Additionally, SIRT1 represses p53 function via deacetylation, promoting tumor growth. Therefore, inhibition of SIRT1 is of great therapeutic interest for the treatment of colon cancer. Here, we report discovery of a novel quinoxaline based small molecule inhibitor of human SIRT1, 4bb, investigated its effect on viability of colon cancer cells and molecular mechanism of action...
May 16, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28526299/mir-200a-regulates-cdk4-6-inhibitor-effect-by-targeting-cdk6-in-metastatic-melanoma
#4
Matias A Bustos, Shigeshi Ono, Diego M Marzese, Takashi Oyama, Yuuki Iida, Garrett Cheung, Nellie Nelson, Sandy C Hsu, Qiang Yu, Dave S B Hoon
Cyclin-dependent kinase (CDK) 4 and 6 pathway is frequently dysregulated in cutaneous melanoma. Recently, CDK4/6 inhibitors have shown promising clinical activity against several cancer types, including melanoma. Here, we demonstrate that miR-200a decreases CDK6 expression and thus reduces the response of CDK4/6 inhibitor in highly proliferative metastatic melanoma. Down-regulation of miR-200a expression in melanoma cells is associated with disease progression and a higher number of lymph node metastases. Furthermore, miR-200a expression is epigenetically modulated by both DNA methylation at the promoter region and chromatin accessibility of an upstream genomic region with enhancer activity...
May 16, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28525852/absolute-quantification-of-dna-methylation-using-microfluidic-chip-based-digital-pcr
#5
Zhenhua Wu, Yanan Bai, Zule Cheng, Fangming Liu, Ping Wang, Dawei Yang, Gang Li, Qinghui Jin, Hongju Mao, Jianlong Zhao
Hypermethylation of CpG islands in the promoter region of many tumor suppressor genes downregulates their expression and in a result promotes tumorigenesis. Therefore, detection of DNA methylation status is a convenient diagnostic tool for cancer detection. Here, we reported a novel method for the integrative detection of methylation by the microfluidic chip-based digital PCR. This method relies on methylation-sensitive restriction enzyme HpaII, which cleaves the unmethylated DNA strands while keeping the methylated ones intact...
May 12, 2017: Biosensors & Bioelectronics
https://www.readbyqxmd.com/read/28524180/aberrant-epigenetic-regulation-of-gabrp-associates-with-aggressive-phenotype-of-ovarian-cancer
#6
Hye Youn Sung, San-Duk Yang, Woong Ju, Jung-Hyuck Ahn
Metastasis is a major cause of therapeutic failure in ovarian cancer. To elucidate molecular mechanisms of ovarian cancer metastasis, we previously established a metastatic xenograft mouse model using human ovarian carcinoma SK-OV-3 cells. Using gene expression profiling, we found that γ-aminobutyric acid (GABA)A receptor π subunit (GABRP) expression was upregulated (>4-fold) in metastatic tissues from our xenograft mice compared with SK-OV-3 cells. Importantly, GABRP knockdown diminished the migration and invasion of SK-OV-3 cells, and reduced extracellular signal-regulated kinase (ERK) activation while overexpression of GABRP exhibited significantly increased cell migration, invasion and ERK activation...
May 19, 2017: Experimental & Molecular Medicine
https://www.readbyqxmd.com/read/28523964/epigenetics-in-endometrial-carcinogenesis-part-2-histone-modifications-chromatin-remodeling-and-noncoding-rnas
#7
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/28522752/mismatch-repair-proteins-initiate-epigenetic-alterations-during-inflammation-driven-tumorigenesis
#8
Ashley R Maiuri, Michael Peng, Shruthi Sriramkumar, Caitlin M Kamplain, Christina DeStefano Shields, Cynthia L Sears, Heather M O'Hagan
Aberrant silencing of genes by DNA methylation contributes to cancer, yet how this process is initiated remains unclear. Using a murine model of inflammation-induced tumorigenesis, we tested the hypothesis that inflammation promotes recruitment of epigenetic proteins to chromatin, initiating methylation and gene silencing in tumors. Compared to normal epithelium and non-inflammation-induced tumors, inflammation-induced tumors gained DNA methylation at CpG islands, some of which are associated with putative tumor suppressor genes...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28521467/upregulation-of-maspin-expression-in-human-cervical-carcinoma-cells-by-transforming-growth-factor-%C3%AE-1-through-the-convergence-of-smad-and-non-smad-signaling-pathways
#9
Ariyaphong Wongnoppavich, Nahathai Dukaew, Sirinthip Choonate, Kongthawat Chairatvit
Mammary serine protease inhibitor (maspin), encoded by the serpin family B member 5 gene, serves as a tumor suppressor through the inhibition of cancer cell invasion and metastasis. Paradoxically, maspin levels are upregulated in a number of types of malignant cells. Therefore, the regulation of maspin expression may depend on the genetic or epigenetic background and the specific microenvironment of carcinoma cells. In the present study, it was demonstrated that transforming growth factor β1 (TGF-β1) induced maspin expression at the transcript and protein levels in the human cervical carcinoma HeLa and human oral squamous carcinoma HSC4 cell lines...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521455/kdm3a-promotes-inhibitory-cytokines-secretion-by-participating-in-tlr4-regulation-of-foxp3-transcription-in-lung-adenocarcinoma-cells
#10
Yinan Li, Wei Yang, Bin Wu, Yaqing Liu, Dongbei Li, Yantong Guo, Haiying Fu, Yi Li
Toll-like receptor 4 (TLR4) is a pattern recognition receptors, a member of the Toll-like receptor family and it serves a role in innate and acquired immunity. It has previously been reported that TLR4 was overexpressed in a variety of tumor tissues and cells, including colorectal cancer, gastric cancer and ovarian cancer. In the tumor microenvironment, the TLR4 signaling pathway may be activated in order to upregulate forkhead box P3 (Foxp3) expression in regulatory T cells (Tregs), and thus enhance the immunosuppressive function of Tregs...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521434/detection-of-spg20-gene-promoter-methylated-dna-as-a-novel-epigenetic-biomarker-in-plasma-for-colorectal-cancer-diagnosis-using-the-methylight-method
#11
Nayebali Rezvani, Reza Alibakhshi, Assad Vaisi-Raygani, Homayoon Bashiri, Massoud Saidijam
Aberrant promoter methylation of genes is a common epigenetic alteration in colorectal cancer (CRC). In the present study, spastic paraplegia 20 (SPG20) promoter-methylated DNA, as a potential diagnostic biomarker, was investigated in plasma and tumor tissue samples from patients with CRC. To the best of our knowledge, the quantification of SPG20 promoter-methylated DNA in plasma samples remains unreported. SPG20 promoter methylation was investigated in 32 paired tumor and healthy adjacent tissues, 37 plasma samples from patients with CRC, and in 37 plasma samples from a healthy control group, using the MethyLight method...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28521327/epigenomics-pharmacoepigenomics-and-personalized-medicine-in-cervical-cancer
#12
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/28521288/hypermethylation-of-ndn-promotes-cell-proliferation-by-activating-the-wnt-signaling-pathway-in-colorectal-cancer
#13
Yu-Han Hu, Qing Chen, Yan-Xia Lu, Jian-Ming Zhang, Chun Lin, Fan Zhang, Wen-Juan Zhang, Xiao-Min Li, Wei Zhang, Xue-Nong Li
The progression of CRC is a multistep process involving several genetic changes or epigenetic modifications. NDN is a member of the MAGE family, encoding a protein that generally suppresses cell proliferation and acting as a transcriptional repressor. Immunohistochemical staining revealed that the expression of NDN was significantly down-regulated in CRC tissues compared with normal tissues and the down-regulation of NDN in CRC could reflect the hypermethylation of the NDN promoter. Treatment of the CRC cell line SW480 with the demethylating agent 5-Aza-CdR restored the NDN expression level...
May 3, 2017: Oncotarget
https://www.readbyqxmd.com/read/28521287/5azadc-treatment-upregulates-mir-375-level-and-represses-hpv16-e6-expression
#14
Adrien Morel, Aurélie Baguet, Jérôme Perrard, Caroline Demeret, Elise Jacquin, David Guenat, Christiane Mougin, Jean-Luc Prétet
High risk human papillomaviruses are the etiological agents of cervical cancer and HPV16 is the most oncogenic genotype. Immortalization and transformation of infected cells requires the overexpression of the two viral oncoproteins E6 and E7 following HPV DNA integration into the host cell genome. Integration often leads to the loss of the E2 open reading frame and the corresponding protein can no longer act as a transcriptional repressor on p97 promoter. Recently, it has been proposed that long control region methylation also contributes to the regulation of E6/E7 expression...
May 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28518147/survivin-a-key-player-in-cancer-progression-increases-in-obesity-and-protects-adipose-tissue-stem-cells-from-apoptosis
#15
Miriam Ejarque, Victòria Ceperuelo-Mallafré, Carolina Serena, Gisela Pachón, Yaiza Núñez-Álvarez, Margarida Terrón-Puig, Enrique Calvo, Catalina Núñez-Roa, Wilfredo Oliva-Olivera, Francisco J Tinahones, Miguel Angel Peinado, Joan Vendrell, Sonia Fernández-Veledo
Adipose tissue (AT) has a central role in obesity-related metabolic imbalance through the dysregulated production of cytokines and adipokines. In addition to its known risk for cardiovascular disease and diabetes, obesity is also a major risk for cancer. We investigated the impact of obesity for the expression of survivin, an antiapoptotic protein upregulated by adipokines and a diagnostic biomarker of tumor onset and recurrence. In a cross-sectional study of 111 subjects classified by body mass index, circulating levels of survivin and gene expression in subcutaneous AT were significantly higher in obese patients and positively correlated with leptin...
May 18, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28518060/analysis-of-healthy-and-tumour-dna-methylation-distributions-in-kidney-renal-clear-cell-carcinoma-using-kullback-leibler-and-jensen-shannon-distance-measures
#16
Nithya Ramakrishnan, Ranjan Bose
DNA methylation is an epigenetic phenomenon in which methyl groups get bonded to the cytosines of the DNA molecule altering the expression of the associated genes. Cancer is linked with hypo or hyper-methylation of specific genes as well as global changes in DNA methylation. In this study, the authors study the probability density function distribution of DNA methylation in various significant genes and across the genome in healthy and tumour samples. They propose a unique 'average healthy methylation distribution' based on the methylation values of several healthy samples...
June 2017: IET Systems Biology
https://www.readbyqxmd.com/read/28517961/overcoming-chemoresistance-in-cancer-stem-cells-with-the-help-of-micrornas-in-colorectal-cancer
#17
Andrew Fesler, Shixiang Guo, Hua Liu, Ning Wu, Jingfang Ju
It has been recognized that acute resistance to chemotherapy mediated by post-transcriptional and translational control is crucial to influence response and survival in cancer treatment. Tumor cells are highly heterogeneous and have the ability to adapt a resistance phenotype through epigenetic regulations such as microRNAs. This poses a major challenge to the treatment of advanced stage colon cancer patients. Colon cancer stem cells have been identified as one of the major contributors to resistance of colon cancer to chemotherapy...
May 18, 2017: Epigenomics
https://www.readbyqxmd.com/read/28516305/arsenic-toxicity-and-epimutagenecity-the-new-lineage
#18
REVIEW
Somnath Paul, Pritha Bhattacharjee, Ashok K Giri, Pritha Bhattacharjee
Global methylation pattern regulates the normal functioning of a cell. Research have shown arsenic alter these methylation landscapes within the genome leading to aberrant gene expression and inducts various pathophysiological outcomes. Long interspersed nuclear elements (LINE-1) normally remains inert due to heavy methylation of it's promoters, time and various environmental insults, they lose these methylation signatures and begin retro-transposition that has been associated with genomic instability and cancerous outcomes...
May 17, 2017: Biometals: An International Journal on the Role of Metal Ions in Biology, Biochemistry, and Medicine
https://www.readbyqxmd.com/read/28516248/environmental-toxicants-incidence-of-degenerative-diseases-and-therapies-from-the-epigenetic-point-of-view
#19
REVIEW
Mahshid Hodjat, Soheila Rahmani, Fazlullah Khan, Kamal Niaz, Mona Navaei-Nigjeh, Solmaz Mohammadi Nejad, Mohammad Abdollahi
Epigenotoxicology is an emerging field of study that investigates the non-genotoxic epigenetic effects of environmental toxicants resulting in alteration of normal gene expression and disruption of cell function. Recent findings on the role of toxicant-induced epigenetic modifications in the development of degenerative diseases have opened up a promising research direction to explore epigenetic therapy approaches and related prognostic biomarkers. In this review, we presented comprehensive data on epigenetic alterations identified in various diseases, including cancer, autoimmune disorders, pulmonary conditions as well as cardiovascular, gastrointestinal and bone disease...
May 17, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28515797/circulating-nucleosomes-as-new-blood-based-biomarkers-for-detection-of-colorectal-cancer
#20
Jean-François Rahier, Anne Druez, Laurence Faugeras, Jean-Paul Martinet, Myriam Géhénot, Eléonore Josseaux, Marielle Herzog, Jake Micallef, Fabienne George, Monique Delos, Thierry De Ronde, Abdenor Badaoui, Lionel D'Hondt
BACKGROUND: Colonoscopy is currently widely accepted as the gold standard for detection of colorectal cancer (CRC) providing detection of up to 95% of pre-cancerous lesions during the procedure. However, certain limitations exist in most countries including cost and access to the procedure. Moreover, colonoscopy is an invasive technique with risk inherent to the endoscopic procedure. For this reason, alternative screening tests, in particular, fecal occult blood-based tests, have been widely adopted for frontline screening...
2017: Clinical Epigenetics
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