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https://www.readbyqxmd.com/read/28211524/epigenetic-and-genetic-dissections-of-uv-induced-global-gene-dysregulation-in-skin-cells-through-multi-omics-analyses
#1
Yao Shen, Milda Stanislauskas, Gen Li, Deyou Zheng, Liang Liu
To elucidate the complex molecular mechanisms underlying the adverse effects UV radiation (UVR) on skin homeostasis, we performed multi-omics studies to characterize UV-induced genetic and epigenetic changes. Human keratinocytes from a single donor treated with or without UVR were analyzed by RNA-seq, exome-seq, and H3K27ac ChIP-seq at 4 h and 72 h following UVR. Compared to the relatively moderate mutagenic effects of UVR, acute UV exposure induced substantial epigenomic and transcriptomic alterations, illuminating a previously underappreciated role of epigenomic and transcriptomic instability in skin pathogenesis...
February 17, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203258/electroacupuncture-at-st36-protects-icc-networks-via-mscf-kit-etv1-signaling-in-the-stomach-of-diabetic-mice
#2
Lugao Tian, Beibei Zhu, Shi Liu
Background. Electroacupuncture (EA) at ST36 has been used to regulate gastric motility and effectively improve gastric emptying in diabetic patients. Nevertheless, the specific mechanisms underlying the efficacy of this treatment remain unknown. The aim of this study was to assess the variations of interstitial cells of Cajal (ICC) and explore the changes in mSCF/KIT-ETV1 signaling in the antrum and corpus of diabetic mice after treatment with EA. Methods. Male C57BL/6 mice were randomized into five groups: control group, diabetic group (DM), diabetic-plus-sham EA group (SEA), diabetic-plus-low-frequency EA group (LEA), and diabetic-plus-high-frequency EA group (HEA)...
2017: Evidence-based Complementary and Alternative Medicine: ECAM
https://www.readbyqxmd.com/read/28186998/somatic-molecular-subtyping-of-prostate-tumors-from-hoxb13-g84e-carriers
#3
Tamara L Lotan, Alba Torres, Miao Zhang, Jeffrey J Tosoian, Liana B Guedes, Helen Fedor, Jessica Hicks, Charles M Ewing, Sarah D Isaacs, Dorhyun Johng, Angelo M De Marzo, William B Isaacs
A recurrent germline mutation (G84E) in the HOXB13 gene is associated with early onset and family history-positive prostate cancer in patients of European descent, occurring in up to 5% of prostate cancer families. To date, the molecular features of prostate tumors occurring in HOXB13 G84E carriers have not been studied in a large cohort of patients. We identified 101 heterozygous carriers of G84E who underwent radical prostatectomy for prostate cancer between 1985 and 2011 and matched these men by race, age and tumor grade to 99 HOXB13 wild-type controls...
February 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28178529/atxn1l-cic-and-ets-transcription-factors-modulate-sensitivity-to-mapk-pathway-inhibition
#4
Belinda Wang, Elsa Beyer Krall, Andrew James Aguirre, Miju Kim, Hans Ragnar Widlund, Mihir Bhavik Doshi, Ewa Sicinska, Rita Sulahian, Amy Goodale, Glenn Spencer Cowley, Federica Piccioni, John Gerard Doench, David Edward Root, William Chun Hahn
Intrinsic resistance and RTK-RAS-MAPK pathway reactivation has limited the effectiveness of MEK and RAF inhibitors (MAPKi) in RAS- and RAF-mutant cancers. To identify genes that modulate sensitivity to MAPKi, we performed genome-scale CRISPR-Cas9 loss-of-function screens in two KRAS mutant pancreatic cancer cell lines treated with the MEK1/2 inhibitor trametinib. Loss of CIC, a transcriptional repressor of ETV1, ETV4, and ETV5, promoted survival in the setting of MAPKi in cancer cells derived from several lineages...
February 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/28167502/a-genetic-interaction-analysis-identifies-cancer-drivers-that-modify-egfr-dependency
#5
Sida Liao, Teresa Davoli, Yumei Leng, Mamie Z Li, Qikai Xu, Stephen J Elledge
A large number of cancer drivers have been identified through tumor sequencing efforts, but how they interact and the degree to which they can substitute for each other have not been systematically explored. To comprehensively investigate how cancer drivers genetically interact, we searched for modifiers of epidermal growth factor receptor (EGFR) dependency by performing CRISPR, shRNA, and expression screens in a non-small cell lung cancer (NSCLC) model. We elucidated a broad spectrum of tumor suppressor genes (TSGs) and oncogenes (OGs) that can genetically modify proliferation and survival of cancer cells when EGFR signaling is altered...
January 15, 2017: Genes & Development
https://www.readbyqxmd.com/read/28161714/structured-and-disordered-regions-cooperatively-mediate-dna-binding-autoinhibition-of-ets-factors-etv1-etv4-and-etv5
#6
Simon L Currie, Desmond K W Lau, Jedediah J Doane, Frank G Whitby, Mark Okon, Lawrence P McIntosh, Barbara J Graves
No abstract text is available yet for this article.
February 6, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28157714/the-role-of-mir-24-as-a-race-related-genetic-factor-in-prostate-cancer
#7
Yutaka Hashimoto, Marisa Shiina, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Varahram Shahryari, Priyanka Kulkarni, Pritha Desgupta, Yozo Mitsui, Mitsuho Sumida, Guoren Deng, Laura Tabatabai, Deepak Kumar, Rajvir Dahiya
The incidence of prostate cancer (PCa) among African-Americans (AfA) is significantly higher than Caucasian-Americans (CaA) but the genetic basis for this disparity is not known. To address this problem, we analyzed miRNA expression in AfA (n = 81) and CaA (n = 51) PCa patients. Here, we found that miR-24 is differentially expressed in AfA and CaA PCa patients and attempt to clarify its role in AfA patients. Also, the public sequencing data of the miR-24 promoter confirmed that it was highly methylated and down-regulated in PCa patients...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28143451/distinct-prostate-cancer-related-mrna-cargo-in-extracellular-vesicle-subsets-from-prostate-cell-lines
#8
Elisa Lázaro-Ibáñez, Taral R Lunavat, Su Chul Jang, Carmen Escobedo-Lucea, Jorge Oliver-De La Cruz, Pia Siljander, Jan Lötvall, Marjo Yliperttula
BACKGROUND: Multiple types of extracellular vesicles (EVs), including microvesicles (MVs) and exosomes (EXOs), are released by all cells constituting part of the cellular EV secretome. The bioactive cargo of EVs can be shuffled between cells and consists of lipids, metabolites, proteins, and nucleic acids, including multiple RNA species from non-coding RNAs to messenger RNAs (mRNAs). In this study, we hypothesized that the mRNA cargo of EVs could differ based on the EV cellular origin and subpopulation analyzed...
February 1, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28039468/differential-expression-of-mir-34b-and-androgen-receptor-pathway-regulate-prostate-cancer-aggressiveness-between-african-americans-and-caucasians
#9
Marisa Shiina, Yutaka Hashimoto, Taku Kato, Soichiro Yamamura, Yuichiro Tanaka, Shahana Majid, Sharanjot Saini, Shahryari Varahram, Priyanka Kulkarni, Pritha Dasgupta, Yozo Mitsui, Mitsuho Sumida, Laura Tabatabai, Guoren Deng, Deepak Kumar, Rajvir Dahiya
African-Americans are diagnosed with more aggressive prostate cancers and have worse survival than Caucasians, however a comprehensive understanding of this health disparity remains unclear. To clarify the mechanisms leading to this disparity, we analyzed the potential involvement of miR-34b expression in African-Americans and Caucasians. miR-34b functions as a tumor suppressor and has a multi-functional role, through regulation of cell proliferation, cell cycle and apoptosis. We found that miR-34b expression is lower in human prostate cancer tissues from African-Americans compared to Caucasians...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/27790742/the-utility-of-etv1-etv4-and-etv5-rna-in-situ-hybridization-in-the-diagnosis-of-cic-dux-sarcomas
#10
Steven C Smith, Nallasivam Palanisamy, Elizabeth Martin, Jorge Almenara, Jonathan B McHugh, Eun-Young K Choi, David R Lucas, Bryan L Betz, Dafydd Thomas, Rajiv M Patel
AIMS: A recently characterized group of undifferentiated small round cell sarcomas harbours fusions of the genes CIC and DUX4. Studies report a distinctive gene expression profile for these sarcomas, including expression of E26 transformation-specific (ETS) family proto-oncogenic transcription factors ETV1, ETV4 and ETV5. To test the utility of an ancillary diagnostic technique for these tumours, we evaluated chromogenic RNA in-situ hybridization assays for ETV1, ETV4 and ETV5 as diagnostic adjuncts for this emerging group of highly malignant sarcomas...
March 2017: Histopathology
https://www.readbyqxmd.com/read/27783944/an-interaction-with-ewing-s-sarcoma-breakpoint-protein-ews-defines-a-specific-oncogenic-mechanism-of-ets-factors-rearranged-in-prostate-cancer
#11
Vivekananda Kedage, Nagarathinam Selvaraj, Taylor R Nicholas, Justin A Budka, Joshua P Plotnik, Travis J Jerde, Peter C Hollenhorst
More than 50% of prostate tumors have a chromosomal rearrangement resulting in aberrant expression of an oncogenic ETS family transcription factor. However, mechanisms that differentiate the function of oncogenic ETS factors expressed in prostate tumors from non-oncogenic ETS factors expressed in normal prostate are unknown. Here, we find that four oncogenic ETS (ERG, ETV1, ETV4, and ETV5), and no other ETS, interact with the Ewing's sarcoma breakpoint protein, EWS. This EWS interaction was necessary and sufficient for oncogenic ETS functions including gene activation, cell migration, clonogenic survival, and transformation...
October 25, 2016: Cell Reports
https://www.readbyqxmd.com/read/27775552/transcription-factor-etv1-is-essential-for-rapid-conduction-in-the-heart
#12
Akshay Shekhar, Xianming Lin, Fang-Yu Liu, Jie Zhang, Huan Mo, Lisa Bastarache, Joshua C Denny, Nancy J Cox, Mario Delmar, Dan M Roden, Glenn I Fishman, David S Park
Rapid impulse propagation in the heart is a defining property of pectinated atrial myocardium (PAM) and the ventricular conduction system (VCS) and is essential for maintaining normal cardiac rhythm and optimal cardiac output. Conduction defects in these tissues produce a disproportionate burden of arrhythmic disease and are major predictors of mortality in heart failure patients. Despite the clinical importance, little is known about the gene regulatory network that dictates the fast conduction phenotype. Here, we have used signal transduction and transcriptional profiling screens to identify a genetic pathway that converges on the NRG1-responsive transcription factor ETV1 as a critical regulator of fast conduction physiology for PAM and VCS cardiomyocytes...
December 1, 2016: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/27633918/an-inhibitor-of-the-acetyltransferases-cbp-p300-exerts-antineoplastic-effects-on-gastrointestinal-stromal-tumor-cells
#13
Meng-Li Gu, Ya-Mei Wang, Xin-Xin Zhou, Hang-Ping Yao, Song Zheng, Zun Xiang, Feng Ji
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasm featured by activated mutations of KIT and PDGFRA. Although overall survival rates have greatly improved by the development of receptor tyrosine kinase inhibitors, most patients ultimately acquire resistance due to secondary mutations of KIT or PDGFRA. Inhibition of the histone acetyltransferases (HATs) CREB‑binding protein (CBP) and p300 results in antineoplastic effects in various cancers. To determine whether CBP/p300 can serve as an antineoplastic target for GISTs, specific short interfering RNA sequences and the selective HAT inhibitor C646 were administered to GIST882 cells...
November 2016: Oncology Reports
https://www.readbyqxmd.com/read/27411289/tert-promoter-mutations-in-pancreatic-endocrine-tumours-are-rare-and-mainly-found-in-tumours-from-patients-with-hereditary-syndromes
#14
João Vinagre, Joana Nabais, Jorge Pinheiro, Rui Batista, Rui Caetano Oliveira, António Pedro Gonçalves, Ana Pestana, Marta Reis, Bárbara Mesquita, Vasco Pinto, Joana Lyra, Maria Augusta Cipriano, Miguel Godinho Ferreira, José Manuel Lopes, Manuel Sobrinho-Simões, Paula Soares
One of the hallmarks of cancer is its unlimited replicative potential that needs a compensatory mechanism for the consequential telomere erosion. Telomerase promoter (TERTp) mutations were recently reported as a novel mechanism for telomerase re-activation/expression in order to maintain telomere length. Pancreatic endocrine tumors (PETs) were so far recognized to rely mainly on the alternative lengthening of telomeres (ALT) mechanism. It was our objective to study if TERTp mutations were present in pancreatic endocrine tumors (PET) and could represent an alternative mechanism to ALT...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27318148/ets-transcription-factor-etv1-regulates-stromal-expansion-and%C3%A2-metastasis-in-pancreatic-cancer
#15
Steffen Heeg, Koushik K Das, Maximilian Reichert, Basil Bakir, Shigetsugu Takano, Julia Caspers, Nicole M Aiello, Katherine Wu, Albrecht Neesse, Anirban Maitra, Christine A Iacobuzio-Donahue, Philip Hicks, Anil K Rustgi
BACKGROUND & AIMS: The ETS-transcription factor ETV1 is involved in epithelial-mesenchymal transition during pancreatic development and is induced in mouse pancreatic intraepithelial neoplasia (PanIN) and pancreatic ductal adenocarcinoma (PDAC). We investigated the function of ETV1 in stromal expansion of PDAC and metastasis, as well as its effects on a novel downstream target Sparc, which encodes a matricellular protein found in PDAC stroma that has been associated with invasiveness, metastasis and poor patient outcomes...
September 2016: Gastroenterology
https://www.readbyqxmd.com/read/27278120/cop1-is-downregulated-in-renal-cell-carcinoma-rcc-and-inhibits-the-migration-of-rcc-achn-cells-in%C3%A2-vitro
#16
La Ta, Chengrui Xuan, Nianzeng Xing, Xiaojun Zhu
Constitutive photomorphogenic 1 (COP1) belongs to the COP‑de-etiolated (DET)‑fusca (FUS) protein family and has been demonstrated to suppress prostate adenocarcinomas and other types of tumor, such as liver and gastric cancer. The present study investigated the expression of COP1 and its downstream factor, ets variant 1 (ETV1) in renal cell carcinoma (RCC) tissue samples, and evaluated the correlation of COP1 expression levels with the clinicopathological characteristics of RCC. In addition, the role of COP1 in the proliferation and migration of RCC ACHN cells was investigated...
August 2016: Molecular Medicine Reports
https://www.readbyqxmd.com/read/27121162/constitutive-photomorphogenesis-protein-1-cop1-and-cop9-signalosome-evolutionarily-conserved-photomorphogenic-proteins-as-possible-targets-of-melatonin
#17
REVIEW
Emilio J Sanchez-Barcelo, Maria D Mediavilla, Jerry Vriend, Russel J Reiter
The ubiquitin proteasome system has been proposed as a possible mechanism involved in the multiple actions of melatonin. COP1 (constitutive photomorphogenesis protein 1), a RING finger-type ubiquitin E3 ligase formerly identified in Arabidopsis, is a central switch for the transition from plant growth underground in darkness (etiolation) to growth under light exposure (photomorphogenesis). In darkness, COP1 binds to photomorphogenic transcription factors driving its degradation via the 26S proteasome; blue light, detected by cryptochromes, and red and far-red light detected by phytochromes, negatively regulate COP1...
August 2016: Journal of Pineal Research
https://www.readbyqxmd.com/read/27059140/the-etv1-transcription-factor-activity-dependently-downregulates-a-set-of-genes-controlling-cell-growth-and-differentiation-in-maturing-cerebellar-granule-cells
#18
Makoto Okazawa, Haruka Abe, Shigetada Nakanishi
In the early postnatal period, cerebellar granule cells exhibit an activity-dependent downregulation of a set of immaturation genes involved in cell growth and migration and are shifted to establishment of a mature network formation. Through the use of a granule cell culture and both pharmacological and RNA interference (siRNA) analyses, the present investigation revealed that the downregulation of these immaturation genes is controlled by strikingly unified signaling mechanisms that operate sequentially through the stimulation of AMPA and NMDA receptors, tetrodotoxin-sensitive Na(+) channels and Ca(2+)/calmodulin-dependent protein kinase II (CaMKII)...
May 13, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/26941328/reciprocal-autoregulation-by-nfi-occupancy-and-etv1-promotes-the-developmental-expression-of-dendrite-synapse-genes-in-cerebellar-granule-neurons
#19
Baojin Ding, John W Cave, Paul R Dobner, Debra Mullikin-Kilpatrick, Marina Bartzokis, Hong Zhu, Chi-Wing Chow, Richard M Gronostajski, Daniel L Kilpatrick
Nuclear Factor One (NFI) transcription factors regulate temporal gene expression required for dendritogenesis and synaptogenesis via delayed occupancy of target promoters in developing cerebellar granule neurons (CGNs). Mechanisms that promote NFI temporal occupancy have not been previously defined. We show here that the transcription factor ETV1 directly binds to and is required for expression and NFI occupancy of a cohort of NFI-dependent genes in CGNs maturing in vivo. Expression of ETV1 is low in early postnatal cerebellum and increases with maturation, mirroring NFI temporal occupancy of coregulated target genes...
May 1, 2016: Molecular Biology of the Cell
https://www.readbyqxmd.com/read/26936919/kit-exon-11-codons-557-558-deletion-mutation-promotes-liver-metastasis-through-the-cxcl12-cxcr4-axis-in-gastrointestinal-stromal-tumors
#20
Hao-Chen Wang, Tzu-Ying Li, Ying-Jui Chao, Ya-Chin Hou, Yuan-Shuo Hsueh, Kai-Hsi Hsu, Yan-Shen Shan
PURPOSE: KIT mutations, the most prevalent genetic event in gastrointestinal stromal tumors (GIST), are associated with malignant features and poor prognosis. Aggressive GISTs possess a high propensity to spread to the liver. This study aimed to explore the role of KIT mutations in GIST liver metastasis. EXPERIMENTAL DESIGN: A total of 170 GISTs were used to determine the association between KIT mutations and liver metastasis. Immunohistochemistry was performed to assess the correlation of KIT mutations with CXCR4 and ETV1 expression...
July 15, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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