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Epigenetic Regulation

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https://www.readbyqxmd.com/read/29156836/the-role-of-rak-in-the-regulation-of-stability-and-function-of-brca1
#1
Jung-Lye Kim, Geun-Hyoung Ha, Loredana Campo, Mitchell F Denning, Tarun B Patel, Clodia Osipo, Shiaw-Yih Lin, Eun-Kyoung Breuer
BRCA1 is an important player in the DNA damage response signaling, and its deficiency results in genomic instability. A complete loss or significantly reduced BRCA1 protein expression is often found in sporadic breast cancer cases despite the absence of genetic or epigenetic aberrations, suggesting the existence of other regulatory mechanisms controlling BRCA1 protein expression. Herein, we demonstrate that Fyn-related kinase (Frk)/Rak plays an important role in maintaining genomic stability, possibly in part through positively regulating BRCA1 protein stability and function via tyrosine phosphorylation on BRCA1 Tyr1552...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156798/arhi-is-a-novel-epigenetic-silenced-tumor-suppressor-in-sporadic-pheochromocytoma
#2
Dong Wang, Li Song, Liang Wang, Lianmei Zhao, Bai Xiang, Ying Li, Baoen Shan, Jing Liu
Pheochromocytoma (PCC) is related to germline mutations in 12 susceptibility genes. Although comparative genomic hybridization array has revealed some putative tumor suppressor genes on the short arm of chromosome 1 that are likely to be involved in PCC tumorigenesis, the molecules involved, except for those encoded by known susceptibility genes, have not been found in the generation of sporadic tumors. In the present work, we first identified that the unmethylated allele of Aplasia Ras homolog member I (ARHI) was deleted in most PCC tumors which retained a hypermethylated copy, while its mRNA level was significantly correlated with the unmethylated copy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156722/whole-exome-sequencing-reveals-novel-mutations-and-epigenetic-regulation-in-hypopharyngeal-carcinoma
#3
Ping Wu, Honglong Wu, Yaoyun Tang, Shi Luo, Xing Fang, Chubo Xie, Jian He, Suping Zhao, Xiaofeng Wang, Jiajia Xu, Xi Chen, Dongfang Li, Huanming Yang, Jian Wang
Hypopharyngeal cancer (HPC) frequently presents at an advanced stage, resulting in poor prognosis. Although combined surgical therapy and chemoradiotherapy have improved the survival for patients with HPC over the past 3 decades, the mortality rate in late-stage diagnosis of HPC is unsatisfactory. In this study, we performed whole-exome sequencing (WES) of 23 hypopharyngeal tumor and paired adjacent normal tissue to identify novel candidate driver genes associated with hypopharyngeal carcinoma. We identified several copy number variants (CNVs) and 15 somatic mutation genes that were associated with hypopharyngeal carcinoma...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156535/hdacis-class-i-cancer-stem-cell-and-phytochemicals-cancer-therapy-and-prevention-implications
#4
REVIEW
Sahar Bayat, Mahmoud Shekari Khaniani, Jalal Choupani, Mohammad Reza Alivand, Sima Mansoori Derakhshan
Epigenetics is independent of the sequence events that physically affect the condensing of chromatin and genes expression. The unique epigenetic memories of various cells trigger exclusive gene expression profiling. According to different studies, the aberrant epigenetic signatures and impaired gene expression profiles are master occurrences in cancer cells in which oncogene and tumor suppressor genes are affected. Owing to the facts that epigenetic modifications are performed earlier than expression and are reversible, the epigenetic reprogramming of cancer cells could be applied potentially for their prevention, control, and therapy...
November 16, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156520/long-noncoding-rna-linc00961-inhibits-cell-invasion-and-metastasis-in-human-non-small-cell-lung-cancer
#5
Bin Jiang, Jing Liu, Yu-Hong Zhang, Dong Shen, Shaoping Liu, Feng Lin, Jun Su, Qing-Feng Lin, Shuai Yan, Yong Li, Wei-Dong Mao, Zhi-Li Liu
Long noncoding RNAs (LncRNAs) expression has been found to be misregulated in multiple human cancers, and a growing number of studies have revealed that lncRNAs can function as important oncogenes or tumor suppressors. In this study, we identified a lncRNA-LINC00961, which was significantly down-regulated in human non-small cell lung cancer tissues. Decreased LINC00961 was associated with NSCLC patients advanced clinical stage, lymph node metastasis, and shorter survival time. Further experiments demonstrated that LSD1 could directly bind to LINC00961 promoter regions and epigenetically repress its transcription in NSCLC cells...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#6
Fernando J Bustos, Estibaliz Ampuero, Nur Jury, Rodrigo Aguilar, Fahimeh Falahi, Jorge Toledo, Juan Ahumada, Jaclyn Lata, Paula Cubillos, Berta Henríquez, Miguel V Guerra, Jimmy Stehberg, Rachael L Neve, Nibaldo C Inestrosa, Ursula Wyneken, Marco Fuenzalida, Steffen Härtel, Miguel Sena-Esteves, Lorena Varela-Nallar, Marianne G Rots, Martin Montecino, Brigitte van Zundert
The Dlg4 gene encodes for post-synaptic density protein 95 (PSD95), a major synaptic protein that clusters glutamate receptors and is critical for plasticity. PSD95 levels are diminished in ageing and neurodegenerative disorders, including Alzheimer's disease and Huntington's disease. The epigenetic mechanisms that (dys)regulate transcription of Dlg4/PSD95, or other plasticity genes, are largely unknown, limiting the development of targeted epigenome therapy. We analysed the Dlg4/PSD95 epigenetic landscape in hippocampal tissue and designed a Dlg4/PSD95 gene-targeting strategy: a Dlg4/PSD95 zinc finger DNA-binding domain was engineered and fused to effector domains to either repress (G9a, Suvdel76, SKD) or activate (VP64) transcription, generating artificial transcription factors or epigenetic editors (methylating H3K9)...
November 16, 2017: Brain: a Journal of Neurology
https://www.readbyqxmd.com/read/29155580/a-unique-approach-to-design-potent-and-selective-cyclic-adenosine-monophosphate-response-element-binding-protein-binding-protein-cbp-inhibitors
#7
Sarah M Bronner, Jeremy M Murray, F Anthony Romero, Kwong Wah Lai, Vickie Tsui, Patrick Cyr, Maureen H Beresini, Gladys de Leon Boenig, Zhongguo Chen, Edna F Choo, Kevin R Clark, Terry D Crawford, Hariharan Jayaram, Susan Kaufman, Ruina Li, Yingjie Li, Jiangpeng Liao, Xiaorong Liang, Wenfeng Liu, Justin Q Ly, Jonathan Maher, John S Wai, Fei Wang, Aijun Zheng, Xiaoyu Zhu, Steven R Magnuson
The epigenetic regulator CBP/P300 presents a novel therapeutic target for oncology. Previously, we reported the development of potent and selective CBP bromodomain inhibitors by first identifying pharmacophores that bind the KAc region, and then building into the LPF shelf. Herein we report the "hybridization" of a variety of KAc-binding fragments with a tetrahydroquinoline scaffold that makes optimal interactions with the LPF shelf, imparting enhanced potency and selectivity to the hybridized ligand. To demonstrate the utility of our hybridization approach, two analogues containing unique Asn binders and the optimized tetrahydroquinoline moiety were rapidly optimized to yield single-digit nanomolar inhibitors of CBP with exquisite selectivity over BRD4(1) and the broader bromodomain family...
November 20, 2017: Journal of Medicinal Chemistry
https://www.readbyqxmd.com/read/29155286/sulfur-mustard-induced-epigenetic-modifications-over-time-a-pilot-study
#8
Thilo Simons, Dirk Steinritz, Birgit Bölck, Annette Schmidt, Tanja Popp, Horst Thiermann, Thomas Gudermann, Wilhelm Bloch, Kai Kehe
The chemical warfare agent sulfur mustard (SM) can cause long-term health effects that may occur even years after a single exposure. The underlying pathophysiology is unknown, but epigenetic mechanisms are discussed as feasible explanation. "Epigenetics" depicts regulation of gene function without affecting the DNA sequence itself. DNA-methylation and covalent histone modifications (methylation or acetylation) are regarded as important processes. In the present in vitro study using early endothelial cells (EEC), we analyzed SM-induced DNA methylation over time and compared results to an in vivo skin sample that was obtained approx...
November 16, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/29155278/mecp2-expression-in-a-rat-model-of-risky-decision-making
#9
Jay V Deng, Caitlin A Orsini, Kristy G Shimp, Barry Setlow
Many neuropsychiatric disorders are associated with abnormal decision making involving risk of punishment, but the underlying molecular basis remains poorly understood. Methyl CpG-binding Protein 2 (MeCP2) is an epigenetic factor that regulates transcription by directly binding to methylated DNA. Here, we evaluated MeCP2 expression in the context of risk-taking behaviors using the Risky Decision-making Task (RDT), in which rats make discrete choices between a small "safe" food reward and a large "risky" food reward accompanied by varying probabilities of punishment...
November 16, 2017: Neuroscience
https://www.readbyqxmd.com/read/29155171/manganese-chloride-induces-histone-acetylation-changes-in-neuronal-cells-its-role-in-manganese-induced-damage
#10
Zhenkun Guo, Zhipeng Zhang, Qingqing Wang, Jie Zhang, Lijin Wang, Qunwei Zhang, Huangyuan Li, Siying Wu
Manganese neurotoxicity presents with Parkinson-like symptoms, with degeneration of dopaminergic neurons in the basal ganglia as the principal pathological feature. Manganese neurotoxicity studies may contribute to a better understanding of the mechanism of Parkinson's disease. Here, we examined the effects of manganese on histone acetylation, a major epigenetic change in chromatin that can regulate gene expression, chromatin remodelling, cell cycle progression, DNA repair and apoptosis. In this study, we found that manganese chloride (MnCl2) may significantly suppress the acetylation of histone H3 and H4 in PC12 cells and SHSY5Y cells in a time-dependent manner...
November 16, 2017: Neurotoxicology
https://www.readbyqxmd.com/read/29155090/proteome-and-phosphoproteome-analysis-of-commensally-induced-dendritic-cell-maturation-states
#11
Ali Giray Korkmaz, Todor Popov, Loulou Peisl, Marius Cosmin Codrea, Sven Nahnsen, Alexander Steimle, Ana Velic, Boris Macek, Martin von Bergen, Joerg Bernhardt, Julia-Stefanie Frick
Dendritic cells (DCs) can shape the immune system towards an inflammatory or tolerant state depending on the bacterial antigens and the environment they encounter. In this study we provide a proteomic catalogue of differentially expressed proteins between distinct DC maturation states, brought about by bacteria that differ in their endotoxicity. To achieve this, we have performed proteomics and phosphoproteomics on murine DC cultures. Symbiont and pathobiont bacteria were used to direct dendritic cells into a semi-mature and fully-mature state, respectively...
November 15, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/29153325/genetic-and-epigenetic-strategies-potentiate-gal4-activation-to-enhance-fitness-in-recently-diverged-yeast-species
#12
Varun Sood, Jason H Brickner
Certain genes show more rapid reactivation for several generations following repression, a conserved phenomenon called epigenetic transcriptional memory. Following previous growth in galactose, GAL gene transcriptional memory confers a strong fitness benefit in Saccharomyces cerevisiae adapting to growth in galactose for up to 8 generations. A genetic screen for mutants defective for GAL gene memory revealed new insights into the molecular mechanism, adaptive consequences, and evolutionary history of memory...
November 9, 2017: Current Biology: CB
https://www.readbyqxmd.com/read/29153168/a-100-year-review-mammary-development-and-lactation
#13
R Michael Akers
What is old is new again-and with respect to the study of the mammary development and function in dairy animals, the expression resonates. Many of the mammary and milk production questions raised in the early years of the Journal of Dairy Science apply today. To be sure, scientists have filled in many details regarding, for example, identification of hormones and growth factors important in the control of mammary growth, the onset of copious milk production at calving, and maintenance of lactation. Early years focused on identification and subsequent availability of classic mammogenic, lactogenic, and galactopoietic hormones (e...
December 2017: Journal of Dairy Science
https://www.readbyqxmd.com/read/29152579/streptococcus-pneumoniae-tigr4-phase-locked-opacity-variants-differ-in-virulence-phenotypes
#14
Melissa B Oliver, Ankita Basu Roy, Ranjit Kumar, Elliot J Lefkowitz, W Edward Swords
Streptococcus pneumoniae (pneumococcus) is a leading human pathogen that can cause serious localized and invasive diseases. Pneumococci can undergo a spontaneous and reversible phase variation that is reflected in colony opacity and which allows the population to adapt to different host environments. Generally, transparent variants are adapted for nasopharyngeal colonization, whereas opaque variants are associated with invasive disease. In recent work, colony phase variation was shown to occur by means of recombination events to generate multiple alleles of the hsdS targeting domain of a DNA methylase complex, which mediates epigenetic changes in gene expression...
November 2017: MSphere
https://www.readbyqxmd.com/read/29152153/molecular-determinants-of-prostate-cancer-metastasis
#15
REVIEW
Kiera Rycaj, Dean G Tang
Metastatic cancer remains largely incurable and fatal. The general course of cancer, from the initiation of primary tumor formation and progression to metastasis, is a multistep process wherein tumor cells at each step must display specific phenotypic features. Distinctive capabilities required for primary tumor initiation and growth form the foundation, and sometimes may remain critical, for subsequent metastases. These phenotypic features must remain easily malleable during the acquisition of additional capabilities unique and essential to the metastatic process such as dissemination to distant tissues wherein tumor cells interact with foreign microenvironments...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29152115/hdac-4-regulates-claudin-2-expression-in-egfr-erk1-2-dependent-manner-to-regulate-colonic-epithelial-cell-differentiation
#16
Rizwan Ahmad, Balawant Kumar, Kaichao Pan, Punita Dhawan, Amar B Singh
In normal colon, claudin-2 expression is restricted to the crypt bottom containing the undifferentiated and proliferative colonocytes. Claudin-2 expression is also upregulated in colorectal cancer (CRC) and promotes carcinogenesis. However, cellular mechanism/s regulated by increased claudin-2 expression during the CRC and mechanism/s regulating this increase remain poorly understood. Epigenetic mechanisms help regulate expression of cancer-associated genes and inhibition of Histone Deacetylases (HDACs) induces cell cycle arrest and differentiation...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151979/effects-of-triple-effective-rna-terna-on-the-inhibition-of-hepatocellular-carcinoma-cells
#17
Yuwen Xue, Tiejun Li, Shuyan Liu, York Yuanyuan Zhu, Guilan Wang, Luyu Fu, Li Chen
The occurrence and development of hepatocellular carcinoma (HCC) is a complicate process involved in genetic mutation and epigenetic regulation. Successful HCC therapy needs multi-targets be involved. The aim of this study was to provide a triple effective RNA (teRNA) which composed of the specific siRNAs targeting NET-1 and VEGF and dsRNA activating TLR3, and explored its anti-HCC roles and mechanism. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence staining, MTT, Annexin V-FITC flow cytometry, Transwell and in-vitro Angiogenesis assay were used to measure the cell biological functions and protein expression analysis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151929/identification-of-circular-rna-signature-in-bladder-cancer
#18
Xiao Yang, Wenbo Yuan, Jun Tao, Peng Li, Chengdi Yang, Xiaheng Deng, Xiaolei Zhang, Jingyuan Tang, Jie Han, Jingzi Wang, Pengchao Li, Qiang Lu, Min Gu
Circular RNA (circRNA) comprises a class of endogenous species of RNA consisting of a circular loop that is crucial for genetic and epigenetic regulation. The significance of circRNA in bladder cancer (BCa) remains to be investigated. Here we performed genome‑wide circRNA analysis of 5 paired tumour and adjacent normal tissue samples from BCa patients via next generation sequencing (NGS) technology. Next we confirmed NGS data in a separate set of 32 paired BCa samples using quantitative real-time reverse transcription polymerase chain reaction...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29151691/parallel-mrna-proteomics-and-mirna-expression-analysis-in-cell-line-models-of-the-intestine
#19
Finbarr O'Sullivan, Joanne Keenan, Sinead Aherne, Fiona O'Neill, Colin Clarke, Michael Henry, Paula Meleady, Laura Breen, Niall Barron, Martin Clynes, Karina Horgan, Padraig Doolan, Richard Murphy
AIM: To identify miRNA-regulated proteins differentially expressed between Caco2 and HT-29: two principal cell line models of the intestine. METHODS: Exponentially growing Caco-2 and HT-29 cells were harvested and prepared for mRNA, miRNA and proteomic profiling. mRNA microarray profiling analysis was carried out using the Affymetrix GeneChip Human Gene 1.0 ST array. miRNA microarray profiling analysis was carried out using the Affymetrix Genechip miRNA 3.0 array...
November 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/29150345/hydrostatic-pressure-as-epigenetic-modulator-in-chondrocyte-cultures-a-study-on-mirna-155-mirna-181a-and-mirna-223-expression-levels
#20
Anna De Palma, Sara Cheleschi, Nicola Antonio Pascarelli, Stefano Giannotti, Mauro Galeazzi, Antonella Fioravanti
Mechanical stimuli and hydrostatic pressure (HP) play an important role in the regulation of chondrocytes metabolism. Growing evidence demonstrated the ability of mechanical loading to modulate the expression of microRNA (miRNA) involved in chondrocytes homeostasis and in the pathogenesis of osteoarthritis (OA). The expression of miR-155, miR-181a and miR-223 in normal and OA chondrocyte cultures, and their potential modifications following exposure to three hours of a cyclic HP (1-5 MPa, frequency 0.25 Hz) were investigated...
November 7, 2017: Journal of Biomechanics
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