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Epigenetics

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https://www.readbyqxmd.com/read/28635682/relationship-between-human-mutl-homolog-1-hmlh1-hypermethylation-and-colorectal-cancer-a-meta-analysis
#1
Hui-Feng Zhang, You-Wang Lu, Zhen-Rong Xie, Kun-Hua Wang
BACKGROUND Hypermethylation of CpG islands in gene promoter regions is an important mechanism of gene inactivation in cancers. Promoter hypermethylation of human mutL homolog 1 (hMLH1) has been implicated in a subset of colorectal cancers that show microsatellite instability (MSI), while the connection of the epigenetic inactivation of hMLH1 in colorectal cancers remains unknown. The aim of this study was to evaluate the relationship between the promoter hypermethylation of hMLH1 and colorectal cancers by performing a meta-analysis...
June 21, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28635355/aberrant-wnt-signaling-a-special-focus-in-cns-diseases
#2
Mercedes Arnés, Sergio Casas Tintó
Wnt signals regulate cell proliferation, migration and differentiation during development, as well as synaptic transmission and plasticity in the adult brain. Abnormal Wnt signaling is central to a number of brain pathologies. We review here, the significance of this pathway focused in the contribution of the most frequent alterations in receptors, secretable modulators and downstream targets in Alzheimer's disease (AD) and Glioblastoma (GBM). β-catenin and GSK3 levels are pivotal in the neurodegeneration associated to AD contributing to memory deficits, tau phosphorylation, increased β-amyloid production and modulation of Apolipoprotein E in the brain...
June 21, 2017: Journal of Neurogenetics
https://www.readbyqxmd.com/read/28635333/molecular-biomarkers-to-guide-precision-medicine-in-localized-prostate-cancer
#3
Minke Smits, Niven Mehra, Michiel Sedelaar, Winald Gerritsen, Jack A Schalken
Major advances through tumor profiling technologies, that include next-generation sequencing, epigenetic, proteomic and transcriptomic methods, have been made in primary prostate cancer, providing novel biomarkers that may guide precision medicine in the near future. Areas covered: The authors provided an overview of novel molecular biomarkers in tissue, blood and urine that may be used as clinical tools to assess prognosis, improve selection criteria for active surveillance programs, and detect disease relapse early in localized prostate cancer...
June 21, 2017: Expert Review of Molecular Diagnostics
https://www.readbyqxmd.com/read/28634396/epigenetic-silencing-of-downstream-genes-mediated-by-tandem-orientation-in-lung-cancer
#4
Steffen Kiehl, Tobias Zimmermann, Rajkumar Savai, Soni S Pullamsetti, Werner Seeger, Marek Bartkuhn, Reinhard H Dammann
Epigenetic deregulation is of importance in tumorigenesis. In particular CpG islands (CGI), are frequently hypermethylated. Here, genome-wide DNA-methylation profiles of 480,000 CpGs in lung cancer cells were generated. It was observed that intra- and intergenic CGI exhibited higher methylation compared to normal cells. The functional annotation of hypermethylated CGI revealed that the hypermethylation was associated with homeobox domain genes and targets marked by repressive histone modifications. The strongest methylation variation was observed in transitional areas of CGI, termed shores...
June 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28634269/human-development-heredity-and-evolution
#5
REVIEW
Ryuichi Nishinakamura, Minoru Takasato
From March 27-29 2017, the RIKEN Center for Developmental Biology held a symposium entitled 'Towards Understanding Human Development, Heredity, and Evolution' in Kobe, Japan. Recent advances in technologies including stem cell culture, live imaging, single-cell approaches, next-generation sequencing and genome editing have led to an expansion in our knowledge of human development. Organized by Yoshiya Kawaguchi, Mitinori Saitou, Mototsugu Eiraku, Tomoya Kitajima, Fumio Matsuzaki, Takashi Tsuji and Edith Heard, the symposium covered a broad range of topics including human germline development, epigenetics, organogenesis and evolution...
June 15, 2017: Development
https://www.readbyqxmd.com/read/28634230/similarity-in-gene-regulatory-networks-suggests-that-cancer-cells-share-characteristics-of-embryonic-neural-cells
#6
Zan Zhang, Anhua Lei, Liyang Xu, Lu Chen, Yonglong Chen, Xuena Zhang, Yan Gao, Xiaoli Yang, Min Zhang, Ying Cao
Cancer cells are immature cells resulting from cellular reprogramming by gene misregulation, and re-differentiation is expected to reduce malignancy. It is unclear, however, whether cancer cells can undergo terminal differentiation. Here, we show that, inhibition of the epigenetic modification enzymes enhancer of zeste homolog 2 (EZH2), histone deacetylases (HDACs) 1 and 3, lysine demethylase 1A (LSD1), or DNA methyltransferase 1 (DNMT1), which all promote cancer development and progression, leads to postmitotic neuron-like differentiation with loss of malignant features in distinct solid cancer cell lines...
June 20, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28634176/impact-of-glycemic-variability-on-chromatin-remodeling-oxidative-stress-and-endothelial-dysfunction-in-type-2-diabetic-patients-with-target-hba1c-levels
#7
Sarah Costantino, Francesco Paneni, Rodolfo Battista, Lorenzo Castello, Giuliana Capretti, Sergio Chiandotto, Luigi Tanese, Giulio Russo, Dario Pitocco, Gaetano A Lanza, Massimo Volpe, Thomas F Lüscher, Francesco Cosentino
Intensive glycemic control (IGC) targeting HbA1c fails to show an unequivocal reduction of macrovascular complications in type 2 diabetes (T2D), however the underlining mechanisms remain elusive. Epigenetic changes are emerging as important mediators of cardiovascular damage and may play a role in this setting. This study investigates whether epigenetic regulation of the adaptor protein p66(Shc), a key driver of mitochondrial oxidative stress, contributes to persistent vascular dysfunction in T2D patients despite IGC...
June 20, 2017: Diabetes
https://www.readbyqxmd.com/read/28634045/egfr-egfrviii-remodels-the-cytoskeleton-via-epigenetic-silencing-of-ajap1-in-glioma-cells
#8
Chao Yang, Yan-Sheng Li, Qi-Xue Wang, Kai Huang, Jian-Wei Wei, Yun-Fei Wang, Jun-Hu Zhou, Kai-Kai Yi, Kai-Liang Zhang, Bing-Cong Zhou, Cong Liu, Liang Zeng, Chun-Sheng Kang
EGFR amplification and mutations are the most common oncogenic events in GBM. EGFR overexpression correlates with GBM invasion, but the underlying mechanisms are poorly understood. In a previous study, we showed that AJAP1 is involved in regulating F-actin to inhibit the invasive ability of GBM. In addition, in a GBM cell line, the AJAP1 promoter was highly bound by H3K27me3 and, through bioinformatics analysis, we found that AJAP1 expression was negatively correlated with EGFR. In this study, we found that the pathway downstream of EGFR had a higher activation level in GBM cell lines, which led to excessive tumor suppressor silencing...
June 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28633955/the-microbiome-and-transfusion-in-cancer-patients
#9
REVIEW
Hadi Goubran, Jerard Seghatchian, Julia Radosevic, Gaafar Ragab, Thierry Burnouf
Our microbiota is determined by many variables including ABO blood groups. The microbiota is not only confined to the gut and skin but is also recoverable from blood of healthy donors. The microbiota shape our immune system through cross reactivity with antigens, the expression of direct molecular patterns, the release of cytokines, the effects on nutrients and micronutrients and even through an interplay with epigenetics. It is likely, therefore, that a donor's microbiota could alter the antigenicity of blood and its components and potentially contribute to transfusion-related immune modulation [TRIM]...
June 3, 2017: Transfusion and Apheresis Science
https://www.readbyqxmd.com/read/28633080/disruptive-non-disruptive-applications-of-crispr-cas9
#10
REVIEW
Jonathan L Schmid-Burgk
The bacterial type II Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-CRISPR Associated (Cas) systems, and in particular Streptococcus pyogenes CRISPR-Cas9, have been broadly applied to edit the genome of bacterial and eukaryotic cells. Cas9, which is an RNA-guided programmable nuclease, is a powerful tool for disrupting protein-coding genes. Cas9 cleaves target sites to generate a double-strand break (DSB) that is repaired via an error-prone repair process, leading to insertion/deletion mutations and gene knockouts...
June 17, 2017: Current Opinion in Biotechnology
https://www.readbyqxmd.com/read/28632820/the-nexus-of-stem-cell-derived-beta-cells-and-genome-engineering
#11
Sara D Sackett, Aida Rodriguez, Jon S Odorico
Diabetes, type 1 and type 2 (T1D and T2D), are diseases of epidemic proportions, which are complicated and defined by genetics, epigenetics, environment, and lifestyle choices. Current therapies consist of whole pancreas or islet transplantation. However, these approaches require life-time immunosuppression, and are compounded by the paucity of available donors. Pluripotent stem cells have advanced research in the fields of stem cell biology, drug development, disease modeling, and regenerative medicine, and importantly allows for the interrogation of therapeutic interventions...
2017: Review of Diabetic Studies: RDS
https://www.readbyqxmd.com/read/28632762/dot1l-inhibitor-improves-early-development-of-porcine-somatic-cell-nuclear-transfer-embryos
#12
Jia Tao, Yu Zhang, Xiaoyuan Zuo, Renyun Hong, Hui Li, Xing Liu, Weiping Huang, Zubing Cao, Yunhai Zhang
Incomplete epigenetic reprogramming of the genome of donor cells causes poor early and full-term developmental efficiency of somatic cell nuclear transfer (SCNT) embryos. Previous research indicate that inhibition of the histone H3 K79 methyltransferase DOT1L, using a selective pharmacological inhibitor EPZ004777 (EPZ), significantly improved reprogramming efficiency during the generation of mouse induced pluripotent stem cells. However, the roles of DOT1L in porcine nuclear transfer-mediated cellular reprogramming are not yet known...
2017: PloS One
https://www.readbyqxmd.com/read/28632718/epigenetic-changes-in-tils
#13
Laurie A Dempsey
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28631608/one-year-in-review-2017-pathogenesis-of-rheumatoid-arthritis
#14
Francesca Angelotti, Alice Parma, Giacomo Cafaro, Riccardo Capecchi, Alessia Alunno, Ilaria Puxeddu
Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease influenced by both genetic and environmental factors. It has been postulated that a high-risk genetic background, in combination with epigenetic marks and environmental exposures, leads to a cascade of events inducing synovitis and consequent destructive arthritis. The clinical picture of joint involvement in RA is the result of chronic inflammation of the synovium, characterised by interactions of resident cells such as fibroblast-like synoviocytes (FLS) with cells of the innate (e...
May 2017: Clinical and Experimental Rheumatology
https://www.readbyqxmd.com/read/28631565/genetic-and-epigenetic-alterations-affecting-park-2-expression-in-cervical-neoplasm-among-north-indian-patients
#15
Afreen Naseem, Zafar Iqbal Bhat, Ponnusamy Kalaiarasan, Bhupender Kumar, Gauri Gandhi, M Moshahid Alam Rizvi
The recent investigation on PARK-2, a putative tumor suppressor gene, has found that it has been altered in multiple human malignancies. However, the clinical impact of PARK-2 alteration in uterine cervix carcinoma has not yet been studied. Therefore, we aimed to examine mutations, promoter hypermethylation, and protein expression of PARK-2 among the North Indian patients and their association with clinical parameters to evaluate the implication of PARK-2 in the genesis of cervical cancer. A total of 168 patient samples were processed for mutational analysis by single-strand conformation polymorphism, sequencing, and further in silico analysis of the identified mutations...
June 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28631441/genetic-landscape-and-deregulated-pathways-in-b-cell-lymphoid-malignancies
#16
R Rosenquist, S Beà, M-Q Du, B Nadel, Q Pan-Hammarström
With the introduction of next-generation sequencing, the genetic landscape of the complex group of B-cell lymphoid malignancies has rapidly been unravelled in recent years. This has provided important information about recurrent genetic events and identified key pathways deregulated in each lymphoma subtype. In parallel, there has been intense search and development of novel types of targeted therapy that 'hit' central mechanisms in lymphoma pathobiology, such as BTK, PI3K or BCL2 inhibitors. In this review, we will outline the current view of the genetic landscape of selected entities: follicular lymphoma, diffuse large B-cell lymphoma, mantle cell lymphoma, chronic lymphocytic leukaemia and marginal zone lymphoma...
June 20, 2017: Journal of Internal Medicine
https://www.readbyqxmd.com/read/28631291/folate-deficiency-disturbs-hsa-let-7-g-level-through-methylation-regulation-in-neural-tube-defects
#17
Li Wang, Shaofang Shangguan, Yu Xin, Shaoyan Chang, Zhen Wang, Xiaolin Lu, Lihua Wu, Bo Niu, Ting Zhang
Folic acid deficiency during pregnancy is believed to be a high-risk factor for neural tube defects (NTDs). Disturbed epigenetic modifications, including miRNA regulation, have been linked to the pathogenesis of NTDs in those with folate deficiency. However, the mechanism by which folic acid-regulated miRNA influences this pathogenesis remains unclear. It is believed that DNA methylation is associated with dysregulated miRNA expression. To clarify this issue, here we measured the methylation changes of 22 miRNAs in 57 human NTD cases to explore whether such changes are involved in miRNA regulation in NTD cases through folate metabolism...
June 19, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28631186/association-between-epidermal-growth-factor-receptor-amplification-and-adp-ribosylation-factor-1-methylation-in-human-glioblastoma
#18
Concha López-Ginés, Lara Navarro, Lisandra Muñoz-Hidalgo, Enrique Buso, José Manuel Morales, Rosario Gil-Benso, Mariela Gregori-Romero, Javier Megías, Pedro Roldán, Remedios Segura-Sabater, José Manuel Almerich-Silla, Daniel Monleón, Miguel Cerdá-Nicolás
PURPOSE: Glioblastoma (GB) is the most frequent and most malignant primary brain tumor in adults. Previously, it has been found that both genetic and epigenetic factors may play critical roles in its etiology and prognosis. In addition, it has been found that the epidermal growth factor receptor gene (EGFR) is frequently over-expressed and amplified in primary GBs. Here, we assessed the promoter methylation status of 10 genes relevant to GB and explored associations between these findings and the EGFR gene amplification status...
June 19, 2017: Cellular Oncology (Dordrecht)
https://www.readbyqxmd.com/read/28631008/regulation-of-neural-circuit-formation-by-protocadherins
#19
REVIEW
Stacey L Peek, Kar Men Mah, Joshua A Weiner
The protocadherins (Pcdhs), which make up the most diverse group within the cadherin superfamily, were first discovered in the early 1990s. Data implicating the Pcdhs, including ~60 proteins encoded by the tandem Pcdha, Pcdhb, and Pcdhg gene clusters and another ~10 non-clustered Pcdhs, in the regulation of neural development have continually accumulated, with a significant expansion of the field over the past decade. Here, we review the many roles played by clustered and non-clustered Pcdhs in multiple steps important for the formation and function of neural circuits, including dendrite arborization, axon outgrowth and targeting, synaptogenesis, and synapse elimination...
June 19, 2017: Cellular and Molecular Life Sciences: CMLS
https://www.readbyqxmd.com/read/28630932/differential-intron-retention-in-jumonji-chromatin-modifier-genes-is-implicated-in-reptile-temperature-dependent-sex-determination
#20
Ira W Deveson, Clare E Holleley, James Blackburn, Jennifer A Marshall Graves, John S Mattick, Paul D Waters, Arthur Georges
In many vertebrates, sex of offspring is determined by external environmental cues rather than by sex chromosomes. In reptiles, for instance, temperature-dependent sex determination (TSD) is common. Despite decades of work, the mechanism by which temperature is converted into a sex-determining signal remains mysterious. This is partly because it is difficult to distinguish the primary molecular events of TSD from the confounding downstream signatures of sexual differentiation. We use the Australian central bearded dragon, in which chromosomal sex determination is overridden at high temperatures to produce sex-reversed female offspring, as a unique model to identify TSD-specific features of the transcriptome...
June 2017: Science Advances
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