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Jian Zhang, Zi-Qi Zheng, Ya-Wei Yuan, Pan-Pan Zhang, Ying-Qin Li, Ya-Qin Wang, Xin-Ran Tang, Xin Wen, Xiao-Hong Hong, Yuan Lei, Qing-Mei He, Xiao-Jing Yang, Ying Sun, Jun Ma, Na Liu
DNA methylation is an important epigenetic change in carcinogenesis. However, the function and mechanism of DNA methylation dysregulation in nasopharyngeal carcinoma (NPC) is still largely unclear. Our previous genome-wide microarray data showed that NFAT1 is one of the most hypermethylated transcription factor genes in NPC tissues. Here, we found that NFAT1 hypermethylation contributes to its down-regulation in NPC. NFAT1 overexpression inhibited cell migration, invasion, and epithelial-mesenchymal transition in vitro and tumor metastasis in vivo...
February 14, 2019: Neoplasia: An International Journal for Oncology Research
D Bellavia, A De Luca, V Carina, V Costa, L Raimondi, F Salamanna, R Alessandro, M Fini, G Giavaresi
MicroRNA (miRNA) has shown to enhance or inhibit cell proliferation, differentiation and activity of different cell types in bone tissue. The discovery of miRNA actions and their targets has helped to identify them as novel regulations actors in bone. Various studies have shown that miRNA deregulation mediates the progression of bone-related pathologies, such as osteoporosis. The present review intends to give an exhaustive overview of miRNAs with experimentally validated targets involved in bone homeostasis and highlight their possible role in osteoporosis development...
February 14, 2019: Bone
Ganesh Acharya, Marisa Bartolomei, Anthony M Carter, Larry Chamley, Charles F Cotton, Junichi Hasegawa, Yuri Hasegawa, Satoshi Hayakawa, Mari Kawaguchi, Chaini Konwar, Shoichi Magawa, Kiyonori Miura, Hirotaka Nishi, Carlos Salomon, Keiichi Sato, Hidenobu Soejima, Hiroaki Soma, Anne Sørensen, Hironori Takahashi, Taketeru Tomita, Camilla M Whittington, Victor Yuan, Perrie O'Tierney-Ginn
Workshops are an important part of the IFPA annual meeting as they allow for discussion of specialized topics. At IFPA meeting 2018 there were nine themed workshops, four of which are summarized in this report. These workshops discussed new knowledge and technological innovations in the following areas of research: 1) viviparity in ocean-living species; 2) placental imaging; 3) epigenetics; and 4) extracellular vesicles in pregnancy.
February 10, 2019: Placenta
Yuqing Yang, Renyi Wu, Davit Sargsyan, Ran Yin, Hsiao-Chen Kuo, Irene Yang, Lujing Wang, David Cheng, Chao Wang, Shanyi Li, Rasika Hudlikar, Yaoping Lu, Ah-Ng Kong
Exposure to ultraviolet B (UVB) irradiation results in multitude of cellular responses including generation of reactive oxygen species and DNA damage and is responsible for non-melanoma skin cancers (NMSCs). Although genetic mutation is well documented, the epi-mutation, the alteration in epigenetics, remains elusive. In this study, we utilized CpG Methyl-seq to identify a genome-wide DNA CpG methylation, to profile the DNA methylation in UVB-irradiated SKH-1 mouse skin epidermis and non-melanoma skin papillomas at various stages...
February 13, 2019: Cancer Letters
Jae Gyun Oh, Seung Pil Jang, Jimeen Yoo, Min-Ah Lee, Seung Hee Lee, Taejoong Lim, Eden Jeong, Changwon Kho, Hyun Kook, Roger J Hajjar, Woo Jin Park, Dongtak Jeong
The reduced expression of cardiac sarco-endoplasmic reticulum Ca2+ ATPase (SERCA2a) is a hallmark of heart failure. We previously showed that miR-25 is a crucial transcriptional regulator of SERCA2a in the heart. However, the precise mechanism of cardiac miR-25 regulation is largely unknown. Literatures suggested that miR-25 is regulated by the transcriptional co-factor, sine oculis homeobox homolog 1 (Six1), which in turn is epigenetically regulated by polycomb repressive complex 2 (PRC 2) in cardiac progenitor cells...
February 13, 2019: Journal of Molecular and Cellular Cardiology
Xu Gao, Xīn Gào, Yan Zhang, Bernd Holleczek, Ben Schöttker, Hermann Brenner
Oxidative stress (OS) has been found to be related to accelerated aging and many aging-related health outcomes. Recently, an epigenetic "mortality risk score" (MS) based on whole blood DNA methylation at 10 mortality-related CpG sites has been demonstrated to be associated with all-cause mortality. This study aimed to address the association between OS and MS, and to assess and compare their performance in the prediction of all-cause mortality. For 1448 participants aged 50-75 of the German ESTHER cohort study, the MS was derived from the DNA methylation profiles measured by Illumina HumanMethylation450K Beadchip and the levels of two urinary OS markers, 8-isoprostane (8-iso) and oxidized guanine/guanosine [including 8-hydroxy-2'-deoxyguanosine (8-oxo)], were measured by ELISA kits...
February 15, 2019: European Journal of Epidemiology
Juliana Imgenberg-Kreuz, Astrid Rasmussen, Kathy Sivils, Gunnel Nordmark
Primary Sjögren's syndrome (pSS) is considered to be a multifactorial disease, where underlying genetic predisposition, epigenetic mechanisms and environmental factors contribute to disease development. In the last 5 years, the first genome-wide association studies in pSS have been completed. The strongest signal of association lies within the HLA genes, whereas the non-HLA genes IRF5 and STAT4 show consistent associations in multiple ethnicities but with a smaller effect size. The majority of the genetic risk variants are found at intergenic regions and their functional impact has in most cases not been elucidated...
February 15, 2019: Rheumatology
Harmen van Andel, Kinga A Kocemba, Marcel Spaargaren, Steven T Pals
Aberrant activation of Wnt/β-catenin signaling plays a central role in the pathogenesis of a wide variety of malignancies and is typically caused by mutations in core Wnt pathway components driving constitutive, ligand-independent signaling. In multiple myelomas (MMs), however, these pathway intrinsic mutations are rare despite the fact that most tumors display aberrant Wnt pathway activity. Recent studies indicate that this activation is caused by genetic and epigenetic lesions of Wnt regulatory components, sensitizing MM cells to autocrine Wnt ligands and paracrine Wnts emanating from the bone marrow niche...
February 15, 2019: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Maik Luu, Sabine Pautz, Vanessa Kohl, Rajeev Singh, Rossana Romero, Sébastien Lucas, Jörg Hofmann, Hartmann Raifer, Niyati Vachharajani, Lucia Campos Carrascosa, Boris Lamp, Andrea Nist, Thorsten Stiewe, Yoav Shaul, Till Adhikary, Mario M Zaiss, Matthias Lauth, Ulrich Steinhoff, Alexander Visekruna
Short-chain fatty acids (SCFAs) have immunomodulatory effects, but the underlying mechanisms are not well understood. Here we show that pentanoate, a physiologically abundant SCFA, is a potent regulator of immunometabolism. Pentanoate induces IL-10 production in lymphocytes by reprogramming their metabolic activity towards elevated glucose oxidation. Mechanistically, this reprogramming is mediated by supplying additional pentanoate-originated acetyl-CoA for histone acetyltransferases, and by pentanoate-triggered enhancement of mTOR activity...
February 15, 2019: Nature Communications
Karen Sugden, Eilis J Hannon, Louise Arseneault, Daniel W Belsky, Jonathan M Broadbent, David L Corcoran, Robert J Hancox, Renate M Houts, Terrie E Moffitt, Richie Poulton, Joseph A Prinz, W Murray Thomson, Benjamin S Williams, Chloe C Y Wong, Jonathan Mill, Avshalom Caspi
Large-scale epigenome-wide association meta-analyses have identified multiple 'signatures'' of smoking. Drawing on these findings, we describe the construction of a polyepigenetic DNA methylation score that indexes smoking behavior and that can be utilized for multiple purposes in population health research. To validate the score, we use data from two birth cohort studies: The Dunedin Longitudinal Study, followed to age-38 years, and the Environmental Risk Study, followed to age-18 years. Longitudinal data show that changes in DNA methylation accumulate with increased exposure to tobacco smoking and attenuate with quitting...
February 15, 2019: Translational Psychiatry
Rodrigo Maldonado, Uwe Schwartz, Elisabeth Silberhorn, Gernot Längst
Chromatin-associated non-coding RNAs modulate the epigenetic landscape and its associated gene expression program. The formation of triple helices is one mechanism of sequence-specific targeting of RNA to chromatin. With this study, we show an important role of the nucleosome and its relative positioning to the triplex targeting site (TTS) in stabilizing RNA-DNA triplexes in vitro and in vivo. Triplex stabilization depends on the histone H3 tail and the location of the TTS close to the nucleosomal DNA entry-exit site...
February 8, 2019: Molecular Cell
Shan-Ju Yeh, Chun-Chieh Yeh, Chung-Yu Lan, Bor-Sen Chen
Candida albicans ( C. albicans ) is the most prevalent fungal species. Although it is a healthy microbiota, genetic and epigenetic alterations in host and pathogen, and microenvironment changes would lead to thrush, vaginal yeast infection, and even hematogenously disseminated infection. Despite the fact that cytotoxicity is well-characterized, few studies discuss the genome-wide genetic and epigenetic molecular mechanisms between host and C. albicans . The aim of this study is to identify drug targets and design a multiple-molecule drug to prevent the infection from C...
February 15, 2019: Toxins
Manar Abu Diab, Rachel Eiges
Fragile X syndrome (FXS) is the most common heritable form of cognitive impairment. It results from a deficiency in the fragile X mental retardation protein (FMRP) due to a CGG repeat expansion in the 5'-UTR of the X-linked FMR1 gene. When CGGs expand beyond 200 copies, they lead to epigenetic gene silencing of the gene. In addition, the greater the allele size, the more likely it will become unstable and exhibit mosaicism for expansion size between and within tissues in affected individuals. The timing and mechanisms of FMR1 epigenetic gene silencing and repeat instability are far from being understood given the lack of appropriate cellular and animal models that can fully recapitulate the molecular features characteristic of the disease pathogenesis in humans...
February 15, 2019: Brain Sciences
G S Araujo, D M S Abessa, A M V M Soares, S Loureiro
To better evaluate chemical damage in chronically contaminated habitats, a nine-generational exposure to Lead (Pb) was done with two monophyletic Daphnia species, from temperate (Daphnia magna) and tropical (Daphnia similis) environments. The multi-generational test consisted generally of a continuous Pb exposed set of organisms, plus an extra control set running simultaneously. To assess daphnids recovery after Pb exposure, some organisms from the sixth generation were transferred to clean media for three extra generations (recovery period; F6 to F9), while others were keep Pb exposed...
February 12, 2019: Ecotoxicology and Environmental Safety
Nicholas D Johnson, Karen N Conneely
A healthy functioning immune system is critical to stave off infectious diseases, but as humans and other organisms age, their immune systems decline. As a result, diseases that were readily thwarted in early life pose nontrivial harm and can even be deadly in late life. Immunosenescence is defined as the general deterioration of the immune system with age, and it is characterized by functional changes in hematopoietic stem cells (HSCs) and specific blood cell types as well as changes in levels of numerous factors, particularly those involved in inflammation...
February 12, 2019: Ageing Research Reviews
Bruno A Cardoso, Teresa L Ramos, Hélio Belo, Filipe Vilas-Boas, Carla Real, António M Almeida
The BCR-ABL-negative myeloproliferative neoplasms (MPN) are driven by JAK-STAT pathway activation but epigenetic alterations also play an important pathophysiological role. These can be pharmacologically manipulated with histone deacetylase inhibitors (HDACis), which have proven to be clinically effective in the treatment of MPN but exhibiting dose-limiting toxicities. The treatment of primary MPN cells with Vorinostat modulates the expression of genes associated with apoptosis, cell cycle, inflammation and signalling...
February 12, 2019: Experimental Hematology
Alberto Marin-Gonzalez, J G Vilhena, Fernando Moreno-Herrero, Ruben Perez
Sequence-dependent DNA conformation and flexibility play a fundamental role in the specificity of DNA-protein interactions. Here we quantify the DNA crookedness: a sequence-dependent deformation of DNA that consists of periodic bends of the base pair centers chain. Using extensive 100  μs-long, all-atom molecular dynamics simulations, we found that DNA crookedness and its associated flexibility are bijective, which unveils a one-to-one relation between DNA structure and dynamics. This allowed us to build a predictive model to compute the stretch moduli of different DNA sequences from solely their structure...
February 1, 2019: Physical Review Letters
Sarah C Pyfrom, Hong Luo, Jacqueline E Payton
BACKGROUND: Long non-coding RNAs (lncRNAs) exhibit remarkable cell-type specificity and disease association. LncRNA's functional versatility includes epigenetic modification, nuclear domain organization, transcriptional control, regulation of RNA splicing and translation, and modulation of protein activity. However, most lncRNAs remain uncharacterized due to a shortage of predictive tools available to guide functional experiments. RESULTS: To address this gap for lymphoma-associated lncRNAs identified in our studies, we developed a new computational method, Predicting LncRNA Activity through Integrative Data-driven 'Omics and Heuristics (PLAIDOH), which has several unique features not found in other methods...
February 15, 2019: BMC Genomics
Jasmine Kaur, Abdelkader Daoud, Scott T Eblen
BACKGROUND: Epigenetic alterations comprise key regulatory events that dynamically alter gene expression and their deregulation is commonly linked to the pathogenesis of various diseases, including cancer. Unlike DNA mutations, epigenetic alterations involve modifications to proteins and nucleic acids that regulate chromatin structure without affecting the underlying DNA sequence, altering the accessibility of the transcriptional machinery to the DNA, thus modulating gene expression. In cancer cells, this often involves the silencing of tumor suppressor genes or the increased expression of genes involved in oncogenesis...
February 14, 2019: Current Molecular Pharmacology
Kevin Dzobo
The human epigenome plays a key role in determining cellular identity and eventually function. Drug discovery undertakings have focused mainly on the role of genomics in carcinogenesis, with the focus turning to the epigenome recently. Drugs targeting DNA and histone modifications are under development with some such as 5-azacytidine, decitabine, vorinostat, and panobinostat already approved by the Food and Drug Administration (FDA) and the European Medicines Agency (EMA). This expert review offers a critical analysis of the epigenomics-guided drug discovery and development and the opportunities and challenges for the next decade...
February 2019: Omics: a Journal of Integrative Biology
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