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https://www.readbyqxmd.com/read/29321666/are-there-multiple-cells-of-origin-of-merkel-cell-carcinoma
#1
REVIEW
J C Sunshine, N S Jahchan, J Sage, J Choi
Merkel cell carcinoma (MCC) is a rare but lethal cancer with the highest case-by-case fatality rate among all skin cancers. Eighty percent of cancers are associated with the Merkel cell polyomavirus (MCPyV). Twenty percent of MCCs are virus negative. Recent epidemiological data suggest that there are important, clinically relevant differences between these two subtypes of MCC. Recent studies in cancer genomics, mouse genetics, and virology experiments have transformed our understanding of MCC pathophysiology...
January 11, 2018: Oncogene
https://www.readbyqxmd.com/read/29317265/wound-regeneration-deficit-in-rats-correlates-with-low-morphogenetic-potential-and-distinct-transcriptome-profile-of-epidermis
#2
Christian F Guerrero-Juarez, Aliaksandr A Astrowski, Rabi Murad, Christina T Dang, Vera O Shatrova, Aksana Astrowskaja, Chae Ho Lim, Raul Ramos, Xiaojie Wang, Yuchen Liu, Hye-Lim Lee, Kim T Pham, Tsai-Ching Hsi, Ji Won Oh, Daniel Crocker, Ali Mortazavi, Mayumi Ito, Maksim V Plikus
Large excisional wounds in mice prominently regenerate new hair follicles (HFs) and fat, yet humans are deficient for this regenerative behavior. Currently, wound-induced regeneration remains a clinically desirable, but only partially understood phenomenon. We show that large excisional wounds in rats, across seven strains fail to regenerate new HFs. We compared wound transcriptomes between mice and rats at the time of scab detachment, which coincides with the onset of HF regeneration in mice. In both species, wound dermis and epidermis share core dermal and epidermal transcriptional programs respectively, yet prominent inter-species differences exist...
January 6, 2018: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29281018/smchd1-haploinsufficiency-exacerbates-the-phenotype-of-a-transgenic-fshd1-mouse-model
#3
Jessica C de Greef, Yvonne D Krom, Bianca den Hamer, Lauren Snider, Yosuke Hiramuki, Rob F P van den Akker, Kelsey Breslin, Miha Pakusch, Daniela C F Salvatori, Bram Slütter, Rabi Tawil, Marnie E Blewitt, Stephen J Tapscott, Silvère M van der Maarel
In humans, a copy of the DUX4 retrogene is located in each unit of the D4Z4 macrosatellite repeat that normally comprises 8-100 units. The D4Z4 repeat has heterochromatic features and does not express DUX4 in somatic cells. Individuals with facioscapulohumeral muscular dystrophy (FSHD) have a partial failure of somatic DUX4 repression resulting in the presence of DUX4 protein in sporadic muscle nuclei. Somatic DUX4 derepression is caused by contraction of the D4Z4 repeat to 1-10 units (FSHD1) or by heterozygous mutations in genes responsible for maintaining the D4Z4 chromatin structure in a repressive state (FSHD2)...
December 21, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/29279330/microrna-146-and-cell-trauma-downregulate-expression-of-the-psoriasis-associated-atypical-chemokine-receptor-ackr2
#4
Kave Shams, Mariola Kurowska-Stolarska, Fabian Schütte, A David Burden, Clive S McKimmie, Gerard J Graham
Chemokines are the principal regulators of leukocyte migration and are essential for initiation and maintenance of inflammation. Atypical chemokine receptor 2 (ACKR2) binds and scavenges proinflammatory CC-chemokines, regulates cutaneous T-cell positioning, and limits the spread of inflammation in vivo. Altered ACKR2 function has been implicated in several inflammatory disorders, including psoriasis, a common and debilitating T cell-driven disorder characterized by thick erythematous skin plaques. ACKR2 expression is abnormal in psoriatic skin, with decreased expression correlating with recruitment of T cells into the epidermis and increased inflammation...
December 26, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29279287/histone-modifiers-dynamic-regulators-of-the-cutaneous-transcriptome
#5
Kanad Ghosh, Kyle O'Neil, Brian C Capell
By regulating the accessibility of the genome, epigenetic regulators such as histone proteins and the chromatin-modifying enzymes that act upon them control gene expression. Proper regulation of this "histone code" allows for the precise control of transcriptional networks that are essential for establishing and maintaining cell fate and identity, disruption of which may drive carcinogenesis. How these dynamic epigenetic regulators contribute to both skin homeostasis and disease is only beginning to be understood...
December 18, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29247660/genome-wide-dna-methylation-profiling-identifies-differential-methylation-in-uninvolved-psoriatic-epidermis
#6
Deepti Verma, Anna-Karin Ekman, Cecilia Bivik Eding, Charlotta Enerbäck
Psoriasis is a chronic inflammatory skin disease with both local and systemic components. Genome-wide approaches have identified more than 60 psoriasis-susceptibility loci, but genes are estimated to explain only one third of the heritability in psoriasis, suggesting additional, yet unidentified, sources of heritability. Epigenetic modifications have been linked to psoriasis and altered DNA methylation patterns in psoriatic versus healthy skin have been reported in whole-skin biopsies. In this study, focusing on epigenetic modifications in the psoriatic uninvolved skin, we compared the lesional and non-lesional epidermis from psoriasis patients with epidermis from healthy controls...
December 13, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/29244975/review-of-the-molecular-mechanisms-in-wound-healing-new-therapeutic-targets
#7
B Palmieri, M Vadalà, C Laurino
The restoration of the skin barrier in acute and chronic wounds is controlled by several molecular mechanisms that synergistically regulate cell kinetics, enzymatic functions, and neurovascular activation. These pathways include genetic and epigenetic activation, which modulate physiological wound healing. Our review describes the genetic background of skin repair, namely transcription-independent diffusible damage signals, individual variability, epigenetic mechanism, controlled qualitative traits, post-translational mechanisms, antioxidants, nutrients, DNA modifications, bacteria activation, mitochondrial activity, and oxidative stress...
December 2, 2017: Journal of Wound Care
https://www.readbyqxmd.com/read/29244109/gadd45a-promotes-active-dna-demethylation-of-the-mmp-9-promoter-via-base-excision-repair-pathway-in-ages-treated-keratinocytes-and-in-diabetic-male-rat-skin
#8
Liyan Zhou, Wei Wang, Chuan Yang, Tingting Zeng, Mengdie Hu, Xiaoyi Wang, Na Li, Kan Sun, Chuan Wang, Jing Zhou, Meng Ren, Li Yan
Diabetes elevates matrix metalloproteinase-9 (MMP-9) levels in the skin and its keratinocytes, and activated MMP-9 impairs skin wound healing. Epigenetic regulation of the DNA methylation status within the MMP-9 promoter plays an important role in the alteration of MMP-9 expression. Our aim was to investigate the role and mechanism of growth arrest and DNA damage-inducible 45a (GADD45a), a well-known DNA demethylation regulatory protein that mediates DNA methylation, in the regulation of MMP-9 expression. In this study, we showed that GADD45a was markedly upregulated in skin tissues from patients with diabetic foot ulcers, in diabetic rats and in human keratinocyte (HaCaT) cells exposed to advanced glycation end products (AGEs)...
December 13, 2017: Endocrinology
https://www.readbyqxmd.com/read/29239787/deciphering-psoriasis-a-bioinformatic-approach
#9
Juan L Melero, Sergi Andrades, Lluís Arola, Antoni Romeu
BACKGROUND: Psoriasis is an immune-mediated, inflammatory and hyperproliferative disease of the skin and joints. The cause of psoriasis is still unknown. The fundamental feature of the disease is the hyperproliferation of keratinocytes and the recruitment of cells from the immune system in the region of the affected skin, which leads to deregulation of many well-known gene expressions. OBJECTIVE: Based on data mining and bioinformatic scripting, here we show a new dimension of the effect of psoriasis at the genomic level...
November 22, 2017: Journal of Dermatological Science
https://www.readbyqxmd.com/read/29232931/molecular-mechanisms-and-management-of-a-cutaneous-inflammatory-disorder-psoriasis
#10
REVIEW
Yu Ri Woo, Dae Ho Cho, Hyun Jeong Park
Psoriasis is a complex chronic inflammatory cutaneous disorder. To date, robust molecular mechanisms of psoriasis have been reported. Among diverse aberrant immunopathogenetic mechanisms, the current model emphasizes the role of Th1 and the IL-23/Th17 axis, skin-resident immune cells and major signal transduction pathways involved in psoriasis. The multiple genetic risk loci for psoriasis have been rapidly revealed with the advent of a novel technology. Moreover, identifying epigenetic modifications could bridge the gap between genetic and environmental risk factors in psoriasis...
December 11, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29180399/diminished-microrna-29b-level-is-associated-with-brd4-mediated-activation-of-oncogenes-in-cutaneous-t-cell-lymphoma
#11
Rebecca Kohnken, Jing Wen, Bethany Mundy-Bosse, Kathleen McConnell, Ashleigh Keiter, Leah Grinshpun, Alex Hartlage, Max Yano, Betina McNeil, Nitin Chakravarti, Basem William, James E Bradner, Michael A Caligiuri, Pierluigi Porcu, Anjali Mishra
MicroRNA dysregulation is a hallmark of cutaneous T-cell lymphoma (CTCL), a uniformly fatal malignancy of skin-homing CD4+ T-cells for which there are few effective therapies. The role of microRNAs (miRs) in controlling epigenetic modifier-dependent transcriptional regulation in CTCL is unknown. In this study, we characterize a novel miR dysregulation contributing to overexpression of epigenetic reader bromodomain-containing protein 4 (BRD4). Using patient CD4+ T-cells, we show diminished levels of miR-29b compared to healthy donor cells...
November 27, 2017: Blood
https://www.readbyqxmd.com/read/29162179/variation-in-dna-methylation-of-the-oxytocin-receptor-gene-predicts-children-s-resilience-to-prenatal-stress
#12
Izabela Milaniak, Charlotte A M Cecil, Edward D Barker, Caroline L Relton, Tom R Gaunt, Wendy McArdle, Sara R Jaffee
Emerging research in epigenetics has shown that there is variability in how environmental exposures "get under the skin" through mechanisms like DNA methylation to influence gene expression that may lead to differential adaptations to stress. This is the first study to examine prospectively the relationship between DNA methylation at birth and resilience to prenatal environmental stressors in several domains (conduct, hyperactivity, emotional problems, and global symptomatology) in middle childhood. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously associated with impairments in social-cognitive processes that may underlie a wide range of childhood psychopathology...
December 2017: Development and Psychopathology
https://www.readbyqxmd.com/read/29161537/association-of-h3k79-monomethylation-an-epigenetic-signature-with-arsenic-induced-skin-lesions
#13
Pritha Bhattacharjee, Somnath Paul, Sandip Bhattacharjee, Ashok K Giri, Pritha Bhattacharjee
Arsenic, a non mutagenic carcinogen, poses a profound health risk upon prolonged exposure. The objective of the study was to analyze the post-translational modifications of the major histone H3 and the associated molecular crosstalk to identify the epigenetic signature of arsenic susceptibility. Herein, we identified significant upregulation of H3K79me1, in individuals with arsenic-induced skin lesion (WSL), and H3K79me1 was found to be regulated by the upstream methyltransferase DOT1L. Moreover, the downstream target molecule 53BP1, a tumor suppressor protein that has a docking preference for H3K79me1 at a site of a double-strand break (DSB), was downregulated, indicating greater DNA damage in the WSL group...
November 14, 2017: Mutation Research
https://www.readbyqxmd.com/read/29156750/somatic-mutations-in-cdh1-and-ctnnb1-in-primary-carcinomas-at-13-anatomic-sites
#14
Evan L Busch, Jason L Hornick, Renato Umeton, Adem Albayrak, Neal I Lindeman, Laura E MacConaill, Elizabeth P Garcia, Matthew Ducar, Timothy R Rebbeck
Metastases are involved in most cancer deaths. Evidence has suggested that cancer cell detachment from primary tumors might occur largely via the mechanism of epithelial-mesenchymal transition (EMT) activated by epigenetic events, but data addressing other possible triggers of detachment, particularly genetic mutations, have been limited. Using the Profile study of cancer genomics at Dana-Farber Cancer Institute, we examined somatic mutations in the EMT genes CDH1 in 5,106 primary carcinomas and CTNNB1 in 7,578 primary carcinomas across 13 anatomic sites: urinary bladder, breast, colon/rectum, endometrium, esophagus, kidney, lung, ovary, pancreas, prostate, skin (non-melanoma), stomach, and thyroid...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29155286/sulfur-mustard-induced-epigenetic-modifications-over-time-a-pilot-study
#15
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/29150847/chronic-sun-exposure-is-associated-with-distinct-histone-acetylation-changes-in-human-skin
#16
S Ding, J Chen, Q Zeng, J Lu, L Tan, A Guo, J Kang, S Yang, Y Xiang, C Zuo, J Huang
BACKGROUND: Photoaging is attributed to continuous sunlight or artificial UV exposure and manifests the clinical and histological changes of skin. Epigenetic changes have been found to be involved in the pathogenesis of photoaging. However, the underlying mechanisms are unclear. OBJECTIVES: To analyse histone modification patterns in sun-exposed and non-exposed skins, and identify the abnormally histone modified-genes related to photoaging. METHODS: Skin biopsies were collected both from the outer forearm (sun-exposed area) and the buttock (sun-protected area) in 20 healthy middle-aged female volunteers...
November 18, 2017: British Journal of Dermatology
https://www.readbyqxmd.com/read/29100458/dna-methylation-hydroxymethylation-in-melanoma
#17
REVIEW
Siqi Fu, Haijing Wu, Huiming Zhang, Christine G Lian, Qianjin Lu
Melanoma is a malignant tumor of melanocytes and is considered to be the most aggressive cancer among all skin diseases. The pathogenesis of melanoma has not been well documented, which may restrict the research and development of biomarkers and therapies. To date, several genetic and epigenetic factors have been identified as contributing to the development and progression of melanoma. Besides the findings on genetic susceptibilities, the recent progress in epigenetic studies has revealed that loss of the DNA hydroxymethylation mark, 5-hydroxymethylcytosine (5-hmC), along with high levels of DNA methylation at promoter regions of several tumor suppressor genes in melanoma, may serve as biomarkers for melanoma...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29070530/the-histone-demethylase-jumonji-domain-containing-protein-3-jmjd3-regulates-fibroblast-activation-in-systemic-sclerosis
#18
Christina Bergmann, Amelie Brandt, Benita Merlevede, Ludwig Hallenberger, Clara Dees, Thomas Wohlfahrt, Sebastian Pötter, Yun Zhang, Chih-Wei Chen, Tatiana Mallano, Ruifang Liang, Rosebeth Kagwiria, Alexander Kreuter, Ioanna Pantelaki, Aline Bozec, David Abraham, Ralf Rieker, Andreas Ramming, Oliver Distler, Georg Schett, Jörg H W Distler
OBJECTIVES: Systemic sclerosis (SSc) fibroblasts remain activated even in the absence of exogenous stimuli. Epigenetic alterations are thought to play a role for this endogenous activation. Trimethylation of histone H3 on lysine 27 (H3K27me3) is regulated by Jumonji domain-containing protein 3 (JMJD3) and ubiquitously transcribed tetratricopeptide repeat on chromosome X (UTX) in a therapeutically targetable manner. The aim of this study was to explore H3K27me3 demethylases as potential targets for the treatment of fibrosis...
October 25, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/29064398/coumestrol-epigenetically-suppresses-cancer-cell-proliferation-coumestrol-is-a-natural-haspin-kinase-inhibitor
#19
Jong-Eun Kim, Sung-Young Lee, Mi Jang, Hyo-Kyung Choi, Jong Hun Kim, Hanyong Chen, Tae-Gyu Lim, Zigang Dong, Ki Won Lee
Targeting epigenetic changes in gene expression in cancer cells may offer new strategies for the development of selective cancer therapies. In the present study, we investigated coumestrol, a natural compound exhibiting broad anti-cancer effects against skin melanoma, lung cancer and colon cancer cell growth. Haspin kinase was identified as a direct target protein of coumestrol using kinase profiling analysis. Histone H3 is a direct substrate of haspin kinase. We observed haspin kinase overexpression as well as greater phosphorylation of histone H3 at threonine 3 (Thr-3) in the cancer cells compared to normal cells...
October 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29044724/tea-polyphenols-for-the-prevention-of-uvb-induced-skin-cancer
#20
REVIEW
Pooja Sharma, Mary Katherine Montes de Oca, Amena R Alkeswani, Sarah F McClees, Tanushree Das, Craig A Elmets, Farrukh Afaq
Skin cancer is the most common type of cancer with increasing incidence rate and public health burden. Solar Ultraviolet (UV) radiation causes an array of damaging cellular and molecular events that eventually lead to the development of skin cancer. Despite increased awareness about sun protection, the exposure rate remains high with less than 15% of men and 30% of women using sunscreen on a regular basis. Therefore, there is an imperative need for the development of novel preventive approaches. Skin cancer chemoprevention using phytochemicals either as dietary supplements or by topical applications has gained considerable attention due to their low toxicity, availability, and anti-carcinogenic properties...
October 16, 2017: Photodermatology, Photoimmunology & Photomedicine
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