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https://www.readbyqxmd.com/read/27920775/human-papillomavirus-downregulates-the-expression-of-ifitm1-and-ripk3-to-escape-from-ifn%C3%AE-and-tnf%C3%AE-mediated-antiproliferative-effects-and-necroptosis
#1
Wenbo Ma, Bart Tummers, Edith M G van Esch, Renske Goedemans, Cornelis J M Melief, Craig Meyers, Judith M Boer, Sjoerd H van der Burg
The clearance of a high-risk human papillomavirus (hrHPV) infection takes time and requires the local presence of a strong type 1 cytokine T cell response, suggesting that hrHPV has evolved mechanisms to resist this immune attack. Using an unique system for non, newly, and persistent hrHPV infection, we show that hrHPV infection renders keratinocytes (KCs) resistant to the antiproliferative- and necroptosis-inducing effects of IFNγ and TNFα. HrHPV-impaired necroptosis was associated with the upregulation of several methyltransferases, including EZH2, and the downregulation of RIPK3 expression...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/27920552/the-relationship-between-the-expression-of-usp22-bmi1-and-ezh2-in-hepatocellular-carcinoma-and-their-impacts-on-prognosis
#2
Run Zhai, Fang Tang, Jianhua Gong, Jing Zhang, Biao Lei, Bo Li, Yangchao Wei, Xingsi Liang, Bo Tang, Songqing He
Recent studies have shown that deubiquitination plays a key role in tumor progression, metastasis, resistance to chemotherapy drugs, and prognosis. In this study, we investigated the effects of the deubiquitinating enzyme USP22 on the expression of the drug-resistance genes BMI1 and EZH2 in hepatocellular carcinoma (HCC) and on prognosis. Downregulation of USP22 expression with interference ribonucleic acid in resistant HCC cell lines with high USP22 expression resulted in decreased BMI1 expression, but had no effect on EZH2 expression...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27913526/update-from-the-latest-who-classification-of-mpns-a-user-s-manual
#3
Francesco Passamonti, Margherita Maffioli
The 2016 multiparameter World Health Organization (WHO) classification for Philadelphia-negative myeloproliferative neoplasms (MPNs) integrates clinical features, morphology, and genetic data to diagnose polycythemia vera (PV), essential thrombocythemia (ET), and primary myelofibrosis (PMF). The main novelties are: (1) the reduction of the hemoglobin (Hb) level threshold to diagnose PV, now established at 16.5 g/dL for men and 16 g/dL for women (based on the identification of MPN patients with PV-consistent bone marrow [BM] features and a Hb level lower than that established in the 2008 WHO classification for PV); (2) the recognition of prefibrotic/early PMF, distinguishable from ET on the basis of BM morphology, an entity having a higher tendency to develop overt myelofibrosis or acute leukemia, and characterized by inferior survival; (3) the central role of BM morphology in the diagnosis of ET, prefibrotic/early PMF, PMF, and PV with borderline Hb values; megakaryocyte number and morphology (typical in ET, atypical in both PMF forms) accompanied by a new distinction of reticulin fibrosis grade in PMF (grade 1 in prefibrotic/early PMF and grade 2-3 in PMF) constitute diagnostic criteria; and (4) the inclusion of all mutually exclusive MPN driver mutations (JAK2, CALR, and MPL) as major diagnostic criteria in ET and PMF; 10% to 15% of these patients are triple negative, and in these cases the search for an additional clonal marker (eg, mutations in ASXL1, EZH2, TET2, IDH1/IDH2, SRSF2, and SF3B1) is warranted...
December 2, 2016: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/27909059/the-role-of-the-histone-methyltransferase-enhancer-of-zeste-homolog-2-ezh2-in-the-pathobiological-mechanisms-underlying-inflammatory-bowel-disease-ibd
#4
Olga F Sarmento, Phyllis A Svingen, Yuning Xiong, Zhifu Sun, Adebowale O Bamidele, Angela J Mathison, Thomas C Smyrk, Asha A Nair, Michelle M Gonzalez, Mary R Sagstetter, Saurabh Baheti, Dermot P B McGovern, Jessica J Friton, Konstantinos A Papadakis, Goel Gautam, Ramnik J Xavier, Raul A Urrutia, William A Faubion
Regulatory T (Treg) cells expressing the transcription factor FOXP3 play a pivotal role in maintaining immunologic self-tolerance. We and others have previously shown that EZH2 is recruited to the FOXP3 promoter and its targets in Treg cells. To further address the role for EZH2 in Treg cellular function, we have now generated mice that lack EZH2 specifically in Treg cells (EZH2ΔFOXP3+). We find that EZH2 deficiency in FOXP3+ T cells results in lethal multi-organ autoimmunity. We further demonstrate that EZH2ΔFOXP3+ T cells lack a regulatory phenotype in vitro and secrete pro-inflammatory cytokines...
December 1, 2016: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/27904778/long-non-coding-rna-ccat2-promotes-gastric-cancer-proliferation-and-invasion-by-regulating-the-e-cadherin-and-lats2
#5
Yong-Jun Wang, Jian-Zhen Liu, Pei Lv, Yi Dang, Jiang-Yan Gao, Yong Wang
Dysregulation of long non-coding RNAs (lncRNAs) play important roles in tumor development and progression. The long non-coding RNA CCAT2 has been identified to be up-regulated in gastric cancer (GC). However, the detailed molecular mechanism of CCAT2 involved in GC progression is still unknown. The aim of this study was to explore the expression and role of CCAT2 in GC progression. In the study, the expression levels of CCAT2 were significantly up-regulated in 108 cases GC tissues compared with adjacent non-tumor tissues by qRT-PCR analysis...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903964/lncrna-h19-inhibits-autophagy-by-epigenetically-silencing-of-diras3-in-diabetic-cardiomyopathy
#6
Chuanjun Zhuo, Ronghuan Jiang, Xiaodong Lin, Mingjing Shao
We previously generated a rat model of diabetic cardiomyopathy and found that the expression of long non-coding RNA H19 was downregulated. The present study was aimed to explore the pathogenic role of H19 in the development of diabetic cardiomyopathy. Overexpression of H19 in diabetic rats attenuated cardiomyocyte autophagy and improved left ventricular function. High glucose was found to reduce H19 expression and increase autophagy in cultured neonatal cardiomyocytes. The results of RNA-binding protein immunoprecipitation showed that H19 could directly bind with EZH2 in cardiomyocytes...
November 26, 2016: Oncotarget
https://www.readbyqxmd.com/read/27902735/role-of-hepatic-specific-transcription-factors-and-polycomb-repressive-complex-2-during-induction-of-fibroblasts-to-hepatic-fate
#7
Shima Rastegar-Pouyani, Niusha Khazaei, Ping Wee, Abdulshakour Mohammadnia, Moein Yaqubi
Direct reprogramming using defined sets of transcription factors (TFs) is a recent strategy for generating induced hepatocytes (iHeps) from fibroblasts for use in regenerative medicine and drug development. Comprehensive studies detailing the regulatory role of TFs during this reprogramming process could help increase its efficiency. This study aimed to find the TFs with the greatest influences on the generation of iHeps from fibroblasts, and to further understand their roles in the regulation of the gene expression program...
2016: PloS One
https://www.readbyqxmd.com/read/27899259/overexpression-of-the-long-non-coding-rna-spry4-it1-promotes-tumor-cell-proliferation-and-invasion-by-activating-ezh2-in-hepatocellular-carcinoma
#8
Meng Zhou, Xiao-Yu Zhang, Xi Yu
BACKGROUND: Increasing evidences have demonstrated that the dysregulation of long non-coding RNAs (lncRNAs) may act as an important role in tumor progression. The long non-coding RNA SPRY4 intronic transcript 1 (SPRY4-IT1) has been reported in some cancer including regulating cell growth, differentiation, apoptosis, and cancer progression. However, the expression and function of SPRY4-IT1 in the progression of hepatocellular carcinoma (HCC) remain largely unknown. METHODS: The lncRNA SPRY4-IT1 was detected by quantitative real time PCR (qRT-PCR) in HCC cell lines, CCK8 cell proliferation and transwell invasion assays were performed to detect the GC cell proliferation and invasion abilities...
November 26, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27897169/ezh1-and-ezh2-promote-skeletal-growth-by-repressing-inhibitors-of-chondrocyte-proliferation-and-hypertrophy
#9
Julian C Lui, Presley Garrison, Quang Nguyen, Michal Ad, Chithra Keembiyehetty, Weiping Chen, Youn Hee Jee, Ellie Landman, Ola Nilsson, Kevin M Barnes, Jeffrey Baron
Histone methyltransferases EZH1 and EZH2 catalyse the trimethylation of histone H3 at lysine 27 (H3K27), which serves as an epigenetic signal for chromatin condensation and transcriptional repression. Genome-wide associated studies have implicated EZH2 in the control of height and mutations in EZH2 cause Weaver syndrome, which includes skeletal overgrowth. Here we show that the combined loss of Ezh1 and Ezh2 in chondrocytes severely impairs skeletal growth in mice. Both of the principal processes underlying growth plate chondrogenesis, chondrocyte proliferation and hypertrophy, are compromised...
November 29, 2016: Nature Communications
https://www.readbyqxmd.com/read/27895750/microrna-298-inhibits-malignant-phenotypes-of-epithelial-ovarian-cancer-by-regulating-the-expression-of-ezh2
#10
Fenmei Zhou, Juan Chen, Hairong Wang
MicroRNA (miRNA or miR)-298 has been reported to be downregulated and to modify the expression of the polycomb protein enhancer of zeste 2 (EZH2) in recurrent epithelial ovarian cancer (EOC). To date, no functional evidence of a miR-298-EZH2 axis in EOC has been documented. The present study aimed to investigate the associations of miR-298 and/or EZH2 expression with clinicopathological features of EOC patients, and revealed their roles in cell motility based on EOC cell lines. Reverse transcription-quantitative polymerase chain reaction was performed to detect the expression levels of miR-298 and EZH2 messenger RNA in human EOC tissues and cell lines...
November 2016: Oncology Letters
https://www.readbyqxmd.com/read/27890434/mir-98-inhibits-hepatocellular-carcinoma-cell-proliferation-via-targeting-ezh2-and-suppressing-wnt-%C3%AE-catenin-signaling-pathway
#11
Jun-Jie Zhang, Jiang-Tao Chen, Long Hua, Kun-Hou Yao, Chen-Yu Wang
Hepatocellular carcinoma (HCC) is a highly aggressive solid malignancy in the word. Aberrant microRNA (miRNA) expression is involved in human diseases including cancer. In the current study, we explore the function of miR-98 in HCC cell proliferation. We found that expression level of miR-98 was significantly decreased in HCC tissues and cells lines compared with adjacent non-tumor issues and human hepatic cell line LO2. Increased expression of miR-98 suppressed HCC cell proliferation and arrested HCC cell cycle in G0/G1 phase...
November 24, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/27889452/an-rb-ezh2-complex-mediates-silencing-of-repetitive-dna-sequences
#12
Charles A Ishak, Aren E Marshall, Daniel T Passos, Carlee R White, Seung J Kim, Matthew J Cecchini, Sara Ferwati, William A MacDonald, Christopher J Howlett, Ian D Welch, Seth M Rubin, Mellissa R W Mann, Frederick A Dick
Repetitive genomic regions include tandem sequence repeats and interspersed repeats, such as endogenous retroviruses and LINE-1 elements. Repressive heterochromatin domains silence expression of these sequences through mechanisms that remain poorly understood. Here, we present evidence that the retinoblastoma protein (pRB) utilizes a cell-cycle-independent interaction with E2F1 to recruit enhancer of zeste homolog 2 (EZH2) to diverse repeat sequences. These include simple repeats, satellites, LINEs, and endogenous retroviruses as well as transposon fragments...
November 12, 2016: Molecular Cell
https://www.readbyqxmd.com/read/27886392/deregulated-expression-of-ezh2-in-congenital-brainstem-disconnection
#13
P G Barth, E Aronica, S Fox, K Fluiter, M A J Weterman, A Poretti, D C Miller, E Boltshauser, B Harding, M Santi, F Baas
Congenital brainstem disconnection (CBSD) is an enigmatic embryo-fetal defect presenting as (sub)total absence of a segment between mesencephalon and lower brainstem. Rostro-caudal limits of the defect vary while the basal pons is always involved and the cerebellum is globally hypoplastic. A recent update and review[1] lists 14 cases, including 3 brain autopsy studies[1-3]. Necrosis and glial- or inflammatory reactions were absent. Inferior olivary nuclei were small or absent, pontine nuclei depleted, and the cerebellar dentate nuclei dysplastic...
November 25, 2016: Neuropathology and Applied Neurobiology
https://www.readbyqxmd.com/read/27882937/ezh2-mediates-lidamycin-induced-cellular-senescence-through-regulating-p21-expression-in-human-colon-cancer-cells
#14
Ming-Quan Sha, Xiao-Li Zhao, Liang Li, Li-Hui Li, Yi Li, Tian-Geng Dong, Wei-Xin Niu, Li-Jun Jia, Rong-Guang Shao, Yong-Su Zhen, Zhen Wang
Lidamycin (LDM) is a novel member of the enediyne antibiotics identified in China with potent antitumor activity. However, it remains unclear whether LDM has potential molecular targets that may affect its antitumor activity. Enhancer of zeste homolog 2 (EZH2) functions as a histone lysine methyltransferase and mediates trimethylation on histone 3 lysine 27 (H3K27me3). High EZH2 level is found to be positively correlated with the aggressiveness, metastasis and poor prognosis of cancer. Here, we aim to study the role of EZH2 in LDM-induced senescence, as well as in the cytotoxicity of LDM in human colon cancer cells...
November 24, 2016: Cell Death & Disease
https://www.readbyqxmd.com/read/27881874/acute-myeloid-leukemia-derived-from-lympho-myeloid-clonal-hematopoiesis
#15
F Thol, S Klesse, L Köhler, R Gabdoulline, A Kloos, A Liebich, M Wichman, A Chaturvedi, J Fabisch, V I Gaidzik, P Paschka, L Bullinger, G Bug, H Serve, G Göhring, B Schlegelberger, M Lübbert, H Kirchner, M Wattad, D Kraemer, B Hertenstein, G Heil, W Fiedler, J Krauter, R Schlenk, K Döhner, H Döhner, A Ganser, M Heuser
We studied acute myeloid leukemia (AML) patients with lympho-myeloid clonal hematopoiesis (LM-CH), defined by the presence of DNA methyltransferase 3A (DNMT3A) mutations in both the myeloid and lymphoid T-cell compartment. Diagnostic, CR and relapse samples were sequenced for 34 leukemia-related genes in 171 DNMT3A mutated adult AML patients. AML with LM-CH was found in 40 patients (23%) and was associated with clonal haematopoiesis of indeterminate potential (CHIP) years prior to AML, older age, secondary AML, and more frequent MDS-type co-mutations (TET2, RUNX1 and EZH2)...
November 24, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27880940/ezh2-overexpression-is-associated-with-poor-prognosis-in-patients-with-glioma
#16
Yanyang Zhang, Xinguang Yu, Ling Chen, Zhibin Zhang, Shiyu Feng
Previous studies have investigated the prognostic value of enhancer of zeste homolog 2 (EZH2) expression in patients with glioma but conclude contradictory results. We aimed to comprehensively evaluate the prognostic role of EZH2 in glioma by meta-analysis. The databases of PubMed, Embase and Web of Science were searched. Hazard ratio (HR) and 95% confidence interval (CI) were combined to assess the association between EZH2 and overall survival (OS) as well as progression-free survival (PFS). Odd ratio (OR) and 95% CI were calculated to investigate the relevance of EZH2 on clinical factors...
November 21, 2016: Oncotarget
https://www.readbyqxmd.com/read/27879367/alternative-splicing-of-ezh2-pre-mrna-by-sf3b3-contributes-to-the-tumorigenic-potential-of-renal-cancer
#17
Ke Chen, Haibing Xiao, Jin Zeng, Gan Yu, Hui Zhou, Chunhua Huang, Weimin Yao, Wei Xiao, Junhui Hu, Wei Guan, Lily Wu, Jiaoti Huang, Qihong Huang, Hua Xu, Zhangqun Ye
PURPOSE: Deregulation or mutation of the EZH2 gene causes various tumors, including ccRCC. Although several splice variants of EZH2 have been identified, little is known about how EZH2 splicing is regulated or the contribution of alternative splicing to its pro-tumorigenic functions. EXPERIMENTAL DESIGN: We conducted RT-PCR, western blot and immunohistochemistry techniques, to examine EZH2 and its alternative splicing transcript expression in renal cancer tissue and renal cancer cell lines...
November 22, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27879268/transcriptional-selectivity-of-epigenetic-therapy-in-cancer
#18
Takahiro Sato, Matteo Cesaroni, Woonbok Chung, Shoghag Panjarian, Anthony Tran, Jozef Madzo, Yasuyuki Okamoto, Hanghang Zhang, Xiaowei Chen, Jaroslav Jelinek, Jean-Pierre J Issa
A central challenge in the development of epigenetic cancer therapy is the ability to direct selectivity in modulating gene expression for disease-selective efficacy. To address this issue, we characterized by RNA-seq, DNA methylation and ChIP-seq analyses the epigenetic response of a set of colon, breast and leukemia cancer cell lines to small molecule inhibitors against DNA methyltransferases (DAC), histone deacetylases (Depsi), histone demethylases (KDM1A inhibitor S2101), and histone methylases (EHMT2 inhibitor UNC0638 and EZH2 inhibitor GSK343)...
November 22, 2016: Cancer Research
https://www.readbyqxmd.com/read/27875550/an-alternative-approach-to-chip-seq-normalization-enables-detection-of-genome-wide-changes-in-histone-h3-lysine-27-trimethylation-upon-ezh2-inhibition
#19
Brian Egan, Chih-Chi Yuan, Madeleine Lisa Craske, Paul Labhart, Gulfem D Guler, David Arnott, Tobias M Maile, Jennifer Busby, Chisato Henry, Theresa K Kelly, Charles A Tindell, Suchit Jhunjhunwala, Feng Zhao, Charlie Hatton, Barbara M Bryant, Marie Classon, Patrick Trojer
Chromatin immunoprecipitation and DNA sequencing (ChIP-seq) has been instrumental in inferring the roles of histone post-translational modifications in the regulation of transcription, chromatin compaction and other cellular processes that require modulation of chromatin structure. However, analysis of ChIP-seq data is challenging when the manipulation of a chromatin-modifying enzyme significantly affects global levels of histone post-translational modifications. For example, small molecule inhibition of the methyltransferase EZH2 reduces global levels of histone H3 lysine 27 trimethylation (H3K27me3)...
2016: PloS One
https://www.readbyqxmd.com/read/27869166/skp2-loss-destabilizes-ezh2-by-promoting-traf6-mediated-ubiquitination-to-suppress-prostate-cancer
#20
W Lu, S Liu, B Li, Y Xie, M G Izban, B R Ballard, S A Sathyanarayana, S E Adunyah, R J Matusik, Z Chen
EZH2 is crucial for the progression of prostate cancer (PCa) and castration-resistant prostate cancer (CRPC) through upregulation and activation of progenitor genes, as well as androgen receptor (AR)-target genes. However, the mechanisms by which EZH2 is regulated in PCa and CRPC remain elusive. Here we report that EZH2 is post-transcriptionally regulated by SKP2 in vitro in cultured cells and in vivo in mouse models. We observed aberrant upregulation of Skp2, Ezh2 and histone H3 lysine 27 trimethylation (H3K27me3) in both Pten null mouse embryonic fibroblasts (MEFs) and Pten null mouse prostate tissues...
November 21, 2016: Oncogene
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