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Epigenetics liver

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https://www.readbyqxmd.com/read/29759938/differentiation-therapy-by-epigenetic-reconditioning-exerts-antitumor-effects-on-liver-cancer-cells
#1
Luc Gailhouste, Lee Chuen Liew, Ken Yasukawa, Izuho Hatada, Yasuhito Tanaka, Hitoshi Nakagama, Takahiro Ochiya
Primary liver tumors are mainly represented by hepatocellular carcinoma (HCC), one of the most aggressive and resistant forms of cancer. Liver tumorigenesis is characterized by an accumulation of epigenetic abnormalities, leading to gene extinction and loss of hepatocyte differentiation. The aim of this work was to investigate the feasibility of converting liver cancer cells toward a less aggressive and differentiated phenotype using a process called epigenetic reconditioning. Here, we showed that an epigenetic regimen with non-cytotoxic doses of the demethylating compound 5-azacytidine (5-AZA) promoted an anti-cancer response by inhibiting HCC cell tumorigenicity...
April 26, 2018: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29751497/epigenetic-regulation-of-atp-binding-cassette-protein-a1-abca1-gene-expression-a-new-era-to-alleviate-atherosclerotic-cardiovascular-disease
#2
Mohamed Zaiou, Ahmed Bakillah
The most important function of high density lipoprotein (HDL) is its ability to remove cholesterol from cells and tissues involved in the early stages of atherosclerosis back to the liver for excretion. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the major part of cholesterol efflux to HDL in macrophage foam cells. Thus, promoting the process of reverse cholesterol transport (RCT) by upregulating mainly ABCA1 remains one of the potential targets for the development of new therapeutic agents against atherosclerosis...
May 3, 2018: Diseases (Basel)
https://www.readbyqxmd.com/read/29748642/gestational-oral-low-dose-estradiol-17%C3%AE-induces-altered-dna-methylation-of-cdkn2d-and-psat1-in-embryos-and-adult-offspring
#3
Vera A van der Weijden, Veronika L Flöter, Susanne E Ulbrich
Endocrine disrupting chemicals (EDC) interfere with the natural hormone balance and may induce epigenetic changes through exposure during sensitive periods of development. In this study, the effects of short-term estradiol-17β (E2) exposure on various tissues of pregnant sows (F0 ) and on day 10 blastocysts (F1 ) were assessed. Intergenerational effects were investigated in the liver of 1-year old female offspring (F1 ). During gestation, sows were orally exposed to two low doses and a high dose of E2 (0.05, 10, and 1000 µg/kg body weight/day)...
May 10, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29747586/selective-modulation-of-local-linkages-between-active-transcription-and-oxidative-demethylation-activity-shapes-cardiomyocyte-specific-gene-body-epigenetic-status-in-mice
#4
Mayumi Oda, Shunichi Wakabayashi, N Ari Wijetunga, Shinsuke Yuasa, Hirokazu Enomoto, Ruri Kaneda, Sung Han Yoon, Nishant Mittal, Qiang Jing, Masako Suzuki, John M Greally, Keiichi Fukuda, Shinji Makino
BACKGROUND: Cell-type-specific genes exhibit heterogeneity in genomic contexts and may be subject to different epigenetic regulations through different gene transcriptional processes depending on the cell type involved. The gene-body regions (GBRs) of some cardiomyocyte (CM)-specific genes are long and highly hypomethylated in CMs. To explore the cell-type specificities of epigenetic patterns and functions, multiple epigenetic modifications of GBRs were compared among CMs, liver cells and embryonic stem cells (ESCs)...
May 10, 2018: BMC Genomics
https://www.readbyqxmd.com/read/29735783/antiproliferative-effects-of-epigenetic-modifier-drugs-through-e-cadherin-up-regulation-in-liver-cancer-cell-lines
#5
Diego Uribe, Andres Cardona, Davide Degli Esposti, Marie-Pierre Cros, Cyrille Cuenin, Zdenko Herceg, Mauricio Camargo, Fabian M Cortés-Mancera
INTRODUCTION: Epigenetic alterations play an essential role in cancer onset and progression, thus studies of drugs targeting the epigenetic machinery are a principal concern for cancer treatment. Here, we evaluated the potential of the combination of the DNA methyltransferase inhibitor 5-aza-2'-deoxycytidine (5aza-dC) and the pan-deacetylase inhibitor Trichostatin A (TSA), at low cytotoxic concentrations, to modulate the canonical Wnt/β-catenin pathway in liver cancer cells. MATERIAL AND METHODS: Pyrosequencing was used for DNA methylation analyses of LINE-1 sequences and the Wnt/β-catenin pathway antagonist DKK3, SFRP1, WIF1 and CDH1...
April 9, 2018: Annals of Hepatology
https://www.readbyqxmd.com/read/29733910/the-contribution-of-cholesterol-and-epigenetic-changes-to-the-pathophysiology-of-breast-cancer
#6
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/29721069/release-of-micrornas-into-body-fluids-from-ten-organs-of-mice-exposed-to-cigarette-smoke
#7
Alberto Izzotti, Mariagrazia Longobardi, Sebastiano La Maestra, Rosanna T Micale, Alessandra Pulliero, Anna Camoirano, Marta Geretto, Francesco D'Agostini, Roumen Balansky, Mark Steven Miller, Vernon E Steele, Silvio De Flora
Purpose : MicroRNAs are small non-coding RNAs that regulate gene expression, thereby playing a role in a variety of physiological and pathophysiological states. Exposure to cigarette smoke extensively downregulates microRNA expression in pulmonary cells of mice, rats, and humans. Cellular microRNAs are released into body fluids, but a poor parallelism was previously observed between lung microRNAs and circulating microRNAs. The purpose of the present study was to validate the application of this epigenetic biomarker by using less invasive collection procedures...
2018: Theranostics
https://www.readbyqxmd.com/read/29718709/intrauterine-programming-mechanism-for-hypercholesterolemia-in-prenatal-caffeine-exposed-female-adult-rat-offspring
#8
Dan Xu, Hanwen W Luo, Wen Hu, Shuwei W Hu, Chao Yuan, Guihua H Wang, Li Zhang, Hong Yu, Jacques Magdalou, Liaobin B Chen, Hui Wang
Clinical and animal studies have indicated that hypercholesterolemia and its associated diseases have intrauterine developmental origins. Our previous studies showed that prenatal caffeine exposure (PCE) led to fetal overexposure to maternal glucocorticoids (GCs) and increased serum total cholesterol levels in adult rat offspring. This study further confirms the intrauterine programming of PCE-induced hypercholesterolemia in female adult rat offspring. Pregnant Wistar rats were intragastrically administered caffeine (30, 60, and 120 mg/kg/d) from gestational day (GD)9 to 20...
May 2, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29691395/epigenetic-landscape-influences-the-liver-cancer-genome-architecture
#9
Natsuko Hama, Yasushi Totoki, Fumihito Miura, Kenji Tatsuno, Mihoko Saito-Adachi, Hiromi Nakamura, Yasuhito Arai, Fumie Hosoda, Tomoko Urushidate, Shoko Ohashi, Wakako Mukai, Nobuyoshi Hiraoka, Hiroyuki Aburatani, Takashi Ito, Tatsuhiro Shibata
The accumulations of different types of genetic alterations such as nucleotide substitutions, structural rearrangements and viral genome integrations and epigenetic alterations contribute to carcinogenesis. Here, we report correlation between the occurrence of epigenetic features and genetic aberrations by whole-genome bisulfite, whole-genome shotgun, long-read, and virus capture sequencing of 373 liver cancers. Somatic substitutions and rearrangement breakpoints are enriched in tumor-specific hypo-methylated regions with inactive chromatin marks and actively transcribed highly methylated regions in the cancer genome...
April 24, 2018: Nature Communications
https://www.readbyqxmd.com/read/29684791/the-role-of-promyelocytic-leukemia-protein-in-steatosis-associated-hepatic-tumors-related-to-chronic-hepatitis-b-virus-infection
#10
Yih-Lin Chung, Mei-Ling Wu
The persistence of hepatitis B surface antigen (HBsAg) is a risk factor for the development of steatosis-associated tumors in chronic hepatitis B virus (HBV) infection, yet little is known about the metabolic link with this factor. We correlated HBV-related pathogenesis in genetically engineered mice and human carriers with metabolic proteomics and lipogenic gene expression profiles. The immunohistochemistry showed that the promyelocytic leukemia protein (PML, a tumor suppressor involved in genome maintenance and fatty acid oxidation), being inversely influenced by the dynamic HBsAg levels from acute phase to seroclearance, appeared as a lipo-metabolic switch linking HBsAg-induced steatosis (lipogenesis) to HBsAg-lost fat-burning hepatocarcinogenesis (lipolysis)...
April 20, 2018: Translational Oncology
https://www.readbyqxmd.com/read/29671161/under-evaluated-or-unassessed-pathogenic-pathways-in-autoimmune-hepatitis-and-implications-for-future-management
#11
REVIEW
Albert J Czaja
Autoimmune hepatitis is a consequence of perturbations in homeostatic mechanisms that maintain self-tolerance but are incompletely understood. The goals of this review are to describe key pathogenic pathways that have been under-evaluated or unassessed in autoimmune hepatitis, describe insights that may shape future therapies, and encourage investigational efforts. The T cell immunoglobulin mucin proteins constitute a family that modulates immune tolerance by limiting the survival of immune effector cells, clearing apoptotic bodies, and expanding the population of granulocytic myeloid-derived suppressor cells...
April 18, 2018: Digestive Diseases and Sciences
https://www.readbyqxmd.com/read/29669855/squalene-epoxidase-drives-nafld-induced-hepatocellular-carcinoma-and-is-a-pharmaceutical-target
#12
Dabin Liu, Chi Chun Wong, Li Fu, Huarong Chen, Liuyang Zhao, Chuangen Li, Yunfei Zhou, Yanquan Zhang, Weiqi Xu, Yidong Yang, Bin Wu, Gong Cheng, Paul Bo-San Lai, Nathalie Wong, Joseph J Y Sung, Jun Yu
Nonalcoholic fatty liver disease (NAFLD)-induced hepatocellular carcinoma (HCC) is an emerging malignancy in the developed world; however, mechanisms that contribute to its formation are largely unknown, and targeted therapy is currently not available. Our RNA sequencing analysis of NAFLD-HCC samples revealed squalene epoxidase ( SQLE ) as the top outlier metabolic gene overexpressed in NAFLD-HCC patients. Hepatocyte-specific Sqle transgenic expression in mice accelerated the development of high-fat, high-cholesterol diet-induced HCC...
April 18, 2018: Science Translational Medicine
https://www.readbyqxmd.com/read/29669510/analysis-of-long-non-coding-rna-lncrna-expression-in-hepatitis-b-patients
#13
Sunde Yılmaz Susluer, Cagla Kayabasi, Besra Ozmen Yelken, Aycan Asik, Didem Celik, Tugce Balci Okcanoglu, Suheyla Serin Senger, Cigir Biray Avci, Sukran Kose, Cumhur Gunduz
Long non-coding RNAs (lncRNAs) have been implicated in numerous biological processes, including epigenetic regulation, cell-cycle control, and transcriptional/translational regulation of gene expression. Differential expression of lncRNAs and disruption of the regulatory processes are recognized as critical steps in cancer development. The role of lncRNAs in hepatitis B virus (HBV) infection is not well understood. Here we analyzed the expression of 135 lncRNAs in plasma samples of 82 HBV patients (classified as chronic patients, inactive carriers, or resolved patients) at diagnosis and at 12 months of treatment in relation to control group (81 healthy volunteers)...
April 19, 2018: Bosnian Journal of Basic Medical Sciences
https://www.readbyqxmd.com/read/29655816/sex-specific-transcription-and-dna-methylation-profiles-of-reproductive-and-epigenetic-associated-genes-in-the-gonads-and-livers-of-breeding-zebrafish
#14
L V Laing, J Viana, E Dempster, T M Uren Webster, R van Aerle, J Mill, E M Santos
Reproduction is an essential process for life and is regulated by complex hormone networks and environmental factors. To date, little is known about the contribution of epigenetic mechanisms to the regulation of reproduction, particularly in lower vertebrates. We used the zebrafish (Danio rerio) model to investigate the sex-specific transcription and DNA methylation profiles for genes involved in the regulation of reproduction and in epigenetic signalling in the livers and gonads. We found evidence for associations between DNA promotor methylation and transcription for esr1 (gonads and female livers), amh (gonads) and dnmt1 (livers)...
April 12, 2018: Comparative Biochemistry and Physiology. Part A, Molecular & Integrative Physiology
https://www.readbyqxmd.com/read/29653269/microrna-26a-is-a-key-regulon-that-inhibits-progression-and-metastasis-of-c-myc-ezh2-double-high-advanced-hepatocellular-carcinoma
#15
Xiang Zhang, Xiao Zhang, Ting Wang, Lei Wang, Zhijun Tan, Wei Wei, Bo Yan, Jing Zhao, Kaichun Wu, Angang Yang, Rui Zhang, Lintao Jia
Overexpressed c-Myc and EZH2 usually mean high malignancy in cancers. Most of mortality from cancer is attributable to metastasis. MicroRNAs(miRNAs), like transcription factors, can regulate hundreds of genes. Here, we identify microRNA-26a (miR-26a) suppresses EZH2 and c-Myc by targeting EZH2 and CDK8 in Wnt pathway. MiR-26a is a well-known tumor-suppressive miRNA in multiple cancers, but how it is downregulated in hepatocellular carcinoma (HCC) is still unclear. Here, we disclose miR-26a is epigenetic silenced by a c-Myc-mediated PRC2-depandent way in HCC...
April 10, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29643477/accurate-estimation-of-5-methylcytosine-in-mammalian-mitochondrial-dna
#16
Shigeru Matsuda, Takehiro Yasukawa, Yuriko Sakaguchi, Kenji Ichiyanagi, Motoko Unoki, Kazuhito Gotoh, Kei Fukuda, Hiroyuki Sasaki, Tsutomu Suzuki, Dongchon Kang
Whilst 5-methylcytosine (5mC) is a major epigenetic mark in the nuclear DNA in mammals, whether or not mitochondrial DNA (mtDNA) receives 5mC modification remains controversial. Herein, we exhaustively analysed mouse mtDNA using three methods that are based upon different principles for detecting 5mC. Next-generation bisulfite sequencing did not give any significant signatures of methylation in mtDNAs of liver, brain and embryonic stem cells (ESCs). Also, treatment with methylated cytosine-sensitive endonuclease McrBC resulted in no substantial decrease of mtDNA band intensities in Southern hybridisation...
April 11, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29627389/plasma-msept9-a-novel-circulating-cell-free-dna-based-epigenetic-biomarker-to-diagnose-hepatocellular-carcinoma
#17
Abderrahim Oussalah, Susann Rischer, Mouni Bensenane, Guillaume Conroy, Pierre Filhine-Tresarrieu, Renée Debard, Denise Forest-Tramoy, Thomas Josse, Dana Reinicke, Matthieu Garcia, Amandine Luc, Cédric Baumann, Ahmet Ayav, Valérie Laurent, Marcus Hollenbach, Cristina Ripoll, Rosa-Maria Guéant-Rodriguez, Fares Namour, Alexander Zipprich, Michael Fleischhacker, Jean-Pierre Bronowicki, Jean-Louis Guéant
BACKGROUND: Patients with cirrhosis are at high risk of hepatocellular carcinoma (HCC). The SEPT9 gene is a key regulator of cell division and tumor suppressor whose hypermethylation is associated with liver carcinogenesis. The primary aim of this study was to evaluate the diagnostic accuracy of a PCR-based assay for the analysis of SEPT9 promoter methylation in circulating cell-free DNA (mSEPT9) for diagnosing HCC among cirrhotic patients. METHODS: We report two phase II biomarker studies that included cirrhotic patients with or without HCC from France (initial study) and Germany (replication study)...
March 28, 2018: EBioMedicine
https://www.readbyqxmd.com/read/29626983/hematopoietic-changes-in-the-offspring-induced-by-maternal-overweight-effect-on-placenta-and-fetal-liver-populations
#18
Luana Leirós, Juliana Barbosa Torreão Dáu, Daphne Pinheiro, Ana Carolina Stumbo Machado, Alessandra Alves Thole, Erika Afonso Costa Cortez, Laís de Carvalho, Simone Nunes de Carvalho
INTRODUCTION: Bone marrow cells (BMC) from obese adult mice display an increased apoptosis rate over proliferation. Hematopoietic stem cells (HSC) form all blood cells and are important BMC used in cell therapy. Because it is known that prenatal development can be affected by adverse metabolic epigenetic programming from the maternal organism, this work aimed to investigate the effects of maternal overweight on placenta and fetal liver hematopoietic niches. METHODS: Overweight was induced in female mice by overfeeding during lactation...
April 2018: Placenta
https://www.readbyqxmd.com/read/29625385/targeting-macrophage-immunometabolism-dawn-in-the-darkness-of-sepsis
#19
REVIEW
V Kumar
Sepsis is known since the time (470 BC) of great Greek physician, Hippocrates. Advancement in modern medicine and establishment of separate branches of medical science dealing with sepsis research have improved its outcome. However, mortality associated with sepsis still remains higher (25-30%) that further increases to 40-50% in the presence of septic shock. For example, sepsis-associated deaths account more in comparison to deaths-associated with myocardial-infarction and certain cancers (i.e. breast and colorectal cancer)...
May 2018: International Immunopharmacology
https://www.readbyqxmd.com/read/29610268/diabetes-mellitus-in-pregnancy-leads-to-growth-restriction-and-epigenetic-modification-of-the-srebf2-gene-in-rat-fetuses
#20
Michaela Golic, Violeta Stojanovska, Ivo Bendix, Anika Wehner, Florian Herse, Nadine Haase, Kristin Kräker, Caroline Fischer, Natalia Alenina, Michael Bader, Till Schütte, Mirjam Schuchardt, Markus van der Giet, Wolfgang Henrich, Dominik N Muller, Ursula Felderhoff-Müser, Sicco Scherjon, Torsten Plösch, Ralf Dechend
Diabetic pregnancy is correlated with increased risk of metabolic and neurological disorders in the offspring putatively mediated epigenetically. Little is known about epigenetic changes already present in fetuses of diabetic pregnancies. We aimed at characterizing the perinatal environment after preexisting maternal diabetes mellitus and at identifying relevant epigenetic changes in the fetus. We focused on the transcription factor Srebf2 (sterol regulatory element binding transcription factor 2), a master gene in regulation of cholesterol metabolism...
April 2, 2018: Hypertension
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