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https://www.readbyqxmd.com/read/29156789/xrcc1-mediated-the-development-of-cervival-cancer-through-a-novel-sp1-krox-20-swich
#1
Qingtao Meng, Shizhi Wang, Weiyan Tang, Shenshen Wu, Na Gao, Chengcheng Zhang, Xiaoli Cao, Xiaobo Li, Zhengdong Zhang, Michael Aschner, Hua Jin, Yue Huang, Rui Chen
Cervical cancer is the second leading cause of mortality among women. Impairment of the base excision repair (BER) pathway is one of the major causes of the initiation and progression of cervical cancer. However, whether the polymorphisms of the BER pathway components (i.e., HOGG1, XRCC1, ADPRT, and APE1) can affect the risk of cervical cancer remains unknown. Herein, we applied a hospital-based case-control study covering two independent cohorts and a subsequent functional assay to determine the roles of the single nucleotide polymorphisms (SNPs) of the BER pathway genes in cervical cancer...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156774/micrornas-as-predictors-for-cns-relapse-of-systemic-diffuse-large-b-cell-lymphoma
#2
Nir Pillar, Osnat Bairey, Neta Goldschmidt, Yakov Fellig, Yevgenia Rosenblat, Itchak Shehtman, Danielle Haguel, Pia Raanani, Noam Shomron, Tali Siegal
Systemic diffuse large B-cell lymphoma (DLBCL) is a potentially curable disease using current regimen of immunochemotherapy. Central nervous system (CNS) relapse is a complication that occurs in approximately 5% of DLBCL patients and is associated with a high fatality rate. Early identification of molecular markers for CNS involvement may serve for the highly needed accurate stratification of patients into risk groups regarding CNS relapse. MicroRNAs (miRNAs) are small non-coding RNA molecules that regulate gene expression at the post-transcriptional level and are known to be involved in DLBCL pathophysiology...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156765/network-directed-cis-mediator-analysis-of-normal-prostate-tissue-expression-profiles-reveals-downstream-regulatory-associations-of-prostate-cancer-susceptibility-loci
#3
Nicholas B Larson, Shannon K McDonnell, Zach Fogarty, Melissa C Larson, John Cheville, Shaun Riska, Saurabh Baheti, Alexandra M Weber, Asha A Nair, Liang Wang, Daniel O'Brien, Jaime Davila, Daniel J Schaid, Stephen N Thibodeau
Large-scale genome-wide association studies have identified multiple single-nucleotide polymorphisms associated with risk of prostate cancer. Many of these genetic variants are presumed to be regulatory in nature; however, follow-up expression quantitative trait loci (eQTL) association studies have to-date been restricted largely to cis-acting associations due to study limitations. While trans-eQTL scans suffer from high testing dimensionality, recent evidence indicates most trans-eQTL associations are mediated by cis-regulated genes, such as transcription factors...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156756/mir-221-regulated-kit-level-by-wild-type-or-leukemia-mutant-runx1-a-determinant-of-single-myeloblast-fate-decisions-that-collectively-drives-or-hinders-granulopoiesis
#4
Stefano Rossetti, Michael J Anauo, Nicoletta Sacchi
RUNX1, a master transcription factor of hematopoiesis, was shown to orchestrate both cell proliferation and differentiation during granulopoiesis by regulating microRNAs (miRs). In this study, taking advantage of the miR-ON reporter system, we monitored first, how the granulocyte colony stimulation factor (GCSF) temporally modulates the concomitant level variation of miR-221 and one of its prototypic targets, the stem cell factor receptor KIT, in single 32D(miR-ON-221) myeloblasts expressing wild type RUNX1...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156748/association-of-melatonin-membrane-receptor-1a-1b-gene-polymorphisms-with-the-occurrence-and-metastasis-of-hepatocellular-carcinoma
#5
Shih-Chi Su, Yung-Chuan Ho, Yu-Fan Liu, Russel J Reiter, Chia-Hsuan Chou, Chia-Ming Yeh, Hsiang-Lin Lee, Wen-Hung Chung, Ming-Ju Hsieh, Shun-Fa Yang
Hepatocellular carcinoma (HCC) is a prevalent primary neoplasm of the liver, whose heterogeneous global incidence suggests the likely impact of genetic variations among individuals on the susceptibility to this disease. Increasing evidence indicates that melatonin exhibits oncostatic properties in many cancer types at least in part mediated by its membrane-bound receptors, melatonin receptor 1A (encoded by MTNR1A) and 1B (MTNR1B). In this study, the effect of melatonin receptor gene polymorphisms on the risk and progression of hepatic tumors was evaluated between 335 HCC patients and 1196 cancer-free subjects...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156689/implications-of-pi3k-akt-inhibition-on-rest-protein-stability-and-neuroendocrine-phenotype-acquisition-in-prostate-cancer-cells
#6
Ruiqui Chen, Yinan Li, Ralph Buttyan, Xuesen Dong
Treatment-induced neuroendocrine prostate cancer (t-NEPC) is an aggressive subtype of prostate cancer (PCa) that arises as a consequence of rigorous androgen receptor (AR) pathway inhibition (ARPI) therapies. While the PI3K/AKT pathway has been investigated as a co-therapeutic target with ARPI for advanced PCa, whether this strategy can prevent tumor progression to t-NEPC remains unknown. Here, we report that PI3K/AKT inhibition alone reduces RE-1 silencing transcription factor (REST) protein expression and induces multiple NE markers in PCa cells...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156655/the-role-of-glyoxalase-i-glo-i-advanced-glycation-endproducts-ages-and-their-receptor-rage-in-chronic-liver-disease-and-hepatocellular-carcinoma-hcc
#7
REVIEW
Marcus Hollenbach
Glyoxalase-I (Glo-I) and glyoxalase-II (Glo-II) comprise the glyoxalase system and are responsible for the detoxification of methylglyoxal (MGO). MGO is formed non-enzymatically as a by-product, mainly in glycolysis, and leads to the formation of advanced glycation endproducts (AGEs). AGEs bind to their receptor, RAGE, and activate intracellular transcription factors, resulting in the production of pro-inflammatory cytokines, oxidative stress, and inflammation. This review will focus on the implication of the Glo-I/AGE/RAGE system in liver injury and hepatocellular carcinoma (HCC)...
November 20, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29156522/the-prevention-of-tnf-%C3%AE-ifn-%C3%AE-mixture-induced-inflammation-in-human-keratinocyte-and-atopic-dermatitis-like-skin-lesions-in-nc-nga-mice-by-mineral-balanced-deep-sea-water
#8
Kyu-Shik Lee, So-Young Chun, Min-Gu Lee, Soyoung Kim, Tae-Jung Jang, Kyung-Soo Nam
Atopic dermatitis (AD) is a chronic inflammatory skin disease caused by environmental and chemical allergens. Despite the complexity of its pathogenesis, many investigations have shown that substances having anti-inflammatory activities alleviated the pathology of AD. Here, we evaluated the effects of mineral-balanced deep sea water (DSW) on AD-like skin damage in both in vitro and in vivo. The results showed that mineral-balanced DSW regressed inflammatory chemokines, such as macrophage-derived chemokine (MDC), thymus- and activation-regulated chemokine (TARC) and regulated on activation, normal T-cell expressed and secreted (RANTES), and cytokines, interleukin (IL)-6 and granulocyte-macrophage colony-stimulating factor (GM-CSF) mRNA expression in HaCaT immortal human keratinocyte treated with tumor necrosis factor (TNF)-α/ interferon (IFN)-γ mixture...
November 14, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/29156375/downregulation-of-the-protein-synthesis-machinery-is-a-major-regulatory-event-during-early-adipogenic-differentiation-of-human-adipose-derived-stromal-cells
#9
Bruna H Marcon, Fabíola B Holetz, Guillermo Eastman, Ana Carolina Origa-Alves, Mariana Andrea Amorós, Alessandra Melo de Aguiar, Carmen K Rebelatto, Paulo R S Brofman, Jose Sotelo-Silveira, Bruno Dallagiovanna
Commitment of adult stem cells involves the activation of specific gene networks regulated from transcription to protein synthesis. Here, we used ribosome profiling to identify mRNAs regulated at the translational level, through both differential association to polysomes and modulation of their translational rates. We observed that translational regulation during the differentiation of human adipose-derived stromal cells (hASCs, also known as adipose-derived mesenchymal stem cells), a subset of which are stem cells, to adipocytes was a major regulatory event...
November 1, 2017: Stem Cell Research
https://www.readbyqxmd.com/read/29156228/effect-of-abiotic-and-biotic-stress-factors-analysis-using-machine-learning-methods-in-zebrafish
#10
Rajasekar Gutha, Suresh Yarrappagaari, Lavanya Thopireddy, Kesireddy Sathyavelu Reddy, Rajeswara Reddy Saddala
In order to understand the mechanisms underlying stress responses, meta-analysis of transcriptome is made to identify differentially expressed genes (DEGs) and their biological, molecular and cellular mechanisms in response to stressors. The present study is aimed at identifying the effect of abiotic and biotic stress factors, and it is found that several stress responsive genes are common for both abiotic and biotic stress factors in zebrafish. The meta-analysis of micro-array studies revealed that almost 4...
November 11, 2017: Comparative Biochemistry and Physiology. Part D, Genomics & Proteomics
https://www.readbyqxmd.com/read/29156207/intracellular-protein-degradation-from-a-vague-idea-thru-the-lysosome-and-the-ubiquitin-proteasome-system-and-onto-human-diseases-and-drug-targeting
#11
REVIEW
Aaron Ciechanover
Between the 1950s and 1980s, scientists were focusing mostly on how the genetic code is transcribed to RNA and translated to proteins, but how proteins are degraded has remained a neglected research area. With the discovery of the lysosome by Christian de Duve it was assumed that cellular proteins are degraded within this organelle. Yet, several independent lines of experimental evidence strongly suggested that intracellular proteolysis is largely non-lysosomal, but the mechanisms involved remained obscure...
December 2017: Best Practice & Research. Clinical Haematology
https://www.readbyqxmd.com/read/29155979/epigenetic-editing-of-the-dlg4-psd95-gene-improves-cognition-in-aged-and-alzheimer-s-disease-mice
#12
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/29155953/max-mutations-in-endometrial-cancer-clinicopathologic-associations-and-recurrent-max-p-his28arg-functional-characterization
#13
Christopher J Walker, Craig M Rush, Paola Dama, Matthew J O'Hern, Casey M Cosgrove, Jessica L Gillespie, Roman A Zingarelli, Blair Smith, Maggie E Stein, David G Mutch, Reena Shakya, Chia-Wen Chang, Karuppaiyah Selvendiran, Jonathan W Song, David E Cohn, Paul J Goodfellow
Background: Genomic studies have revealed that multiple genes are mutated at varying frequency in endometrial cancer (EC); however, the relevance of many of these mutations is poorly understood. An EC-specific recurrent mutation in the MAX transcription factor p.His28Arg was recently discovered. We sought to assess the functional consequences of this hotspot mutation and determine its association with cancer-relevant phenotypes. Methods: MAX was sequenced in 509 endometrioid ECs, and associations between mutation status and clinicopathologic features were assessed...
November 15, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29155882/pharmacological-inhibition-of-ror%C3%AE-t-suppresses-the-th17-pathway-and-alleviates-arthritis-in-vivo
#14
Ulf Guendisch, Jessica Weiss, Florence Ecoeur, Julia Christina Riker, Klemens Kaupmann, Joerg Kallen, Samuel Hintermann, David Orain, Janet Dawson, Andreas Billich, Christine Guntermann
Retinoic acid receptor-related-orphan-receptor-C (RORγt) is the key transcription factor that is driving the differentiation of IL-17 producing T-helper 17 (Th17) cells that are implicated in the pathology of various autoimmune and inflammatory diseases. Based on the importance of RORγt in promoting Th17-driven pathology, there is considerable interest to develop low-molecular-weight compounds with the aim of inhibiting the transcriptional activity of this nuclear hormone receptor. In this article, we describe the in vitro and in vivo pharmacology of a potent and selective small-molecular-weight RORγt inverse agonist...
2017: PloS One
https://www.readbyqxmd.com/read/29155844/hypoxia-and-hypoxia-inducible-factor-hif-downregulate-antigen-presenting-mhc-class-i-molecules-limiting-tumor-cell-recognition-by-t-cells
#15
Shalini Sethumadhavan, Murillo Silva, Phaethon Philbrook, Thao Nguyen, Stephen M Hatfield, Akio Ohta, Michail V Sitkovsky
Human cancers are known to downregulate Major Histocompatibility Complex (MHC) class I expression thereby escaping recognition and rejection by anti-tumor T cells. Here we report that oxygen tension in the tumor microenvironment (TME) serves as an extrinsic cue that regulates antigen presentation by MHC class I molecules. In support of this view, hypoxia is shown to negatively regulate MHC expression in a HIF-dependent manner as evidenced by (i) lower MHC expression in the hypoxic TME in vivo and in hypoxic 3-dimensional (3D) but not 2-dimensional (2D) tumor cell cultures in vitro; (ii) decreased MHC in human renal cell carcinomas with constitutive expression of HIF due to genetic loss of von Hippel-Lindau (VHL) function as compared with isogenically paired cells with restored VHL function, and iii) increased MHC in tumor cells with siRNA-mediated knockdown of HIF...
2017: PloS One
https://www.readbyqxmd.com/read/29155828/role-of-co-repressor-genomic-landscapes-in-shaping-the-notch-response
#16
Stephen K K Chan, Gustavo Cerda-Moya, Robert Stojnic, Kat Millen, Bettina Fischer, Silvie Fexova, Lenka Skalska, Maria Gomez-Lamarca, Zoe Pillidge, Steven Russell, Sarah J Bray
Repressors are frequently deployed to limit the transcriptional response to signalling pathways. For example, several co-repressors interact directly with the DNA-binding protein CSL and are proposed to keep target genes silenced in the absence of Notch activity. However, the scope of their contributions remains unclear. To investigate co-repressor activity in the context of this well defined signalling pathway, we have analysed the genome-wide binding profile of the best-characterized CSL co-repressor in Drosophila, Hairless, and of a second CSL interacting repressor, SMRTER...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155818/snail1-mediated-downregulation-of-foxa-proteins-facilitates-the-inactivation-of-transcriptional-enhancer-elements-at-key-epithelial-genes-in-colorectal-cancer-cells
#17
Sabine Jägle, Hauke Busch, Vivien Freihen, Sven Beyes, Monika Schrempp, Melanie Boerries, Andreas Hecht
Phenotypic conversion of tumor cells through epithelial-mesenchymal transition (EMT) requires massive gene expression changes. How these are brought about is not clear. Here we examined the impact of the EMT master regulator SNAIL1 on the FOXA family of transcription factors which are distinguished by their particular competence to induce chromatin reorganization for the activation of transcriptional enhancer elements. We show that the expression of SNAIL1 and FOXA genes is anticorrelated in transcriptomes of colorectal tumors and cell lines...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155810/regulation-of-transcription-elongation-in-response-to-osmostress
#18
Andrea Silva, Santiago Cavero, Victoria Sarah, Carme Solé, René Böttcher, Sebastián Chávez, Francesc Posas, Eulàlia de Nadal
Cells trigger massive changes in gene expression upon environmental fluctuations. The Hog1 stress-activated protein kinase (SAPK) is an important regulator of the transcriptional activation program that maximizes cell fitness when yeast cells are exposed to osmostress. Besides being associated with transcription factors bound at target promoters to stimulate transcriptional initiation, activated Hog1 behaves as a transcriptional elongation factor that is selective for stress-responsive genes. Here, we provide insights into how this signaling kinase functions in transcription elongation...
November 20, 2017: PLoS Genetics
https://www.readbyqxmd.com/read/29155791/improved-protocol-for-chromatin-immunoprecipitation-from-mouse-skeletal-muscle
#19
Shilpy Joshi, Vanessa Ueberschlag-Pitiot, Daniel Metzger, Irwin Davidson
We describe an efficient and reproducible protocol for the preparation of chromatin from adult mouse skeletal muscle, a physically resistant tissue with a high content of structural proteins. Dissected limb muscles from adult mice are physically disrupted by mechanical homogenisation, or a combination of mincing and douncing, in a hypotonic buffer before formaldehyde fixation of the cell lysate. The fixed nuclei are purified by further cycles of mechanical homogenisation or douncing and sequential filtrations to remove cell debris...
November 6, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29155775/mapping-genome-wide-accessible-chromatin-in-primary-human-t-lymphocytes-by-atac-seq
#20
Ivana Grbesa, Miriam Tannenbaum, Avital Sarusi-Portuguez, Michal Schwartz, Ofir Hakim
Assay for Transposase-Accessible Chromatin with high-throughput sequencing (ATAC-seq) is a method used for the identification of open (accessible) regions of chromatin. These regions represent regulatory DNA elements (e.g., promoters, enhancers, locus control regions, insulators) to which transcription factors bind. Mapping the accessible chromatin landscape is a powerful approach for uncovering active regulatory elements across the genome. This information serves as an unbiased approach for discovering the network of relevant transcription factors and mechanisms of chromatin structure that govern gene expression programs...
November 13, 2017: Journal of Visualized Experiments: JoVE
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