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epigenetic silence

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https://www.readbyqxmd.com/read/29161428/arabidopsis-inositol-polyphosphate-multikinase-delays-flowering-time-through-mediating-transcriptional-activation-of-flowering-locus-c
#1
Sihong Sang, Yao Chen, Qiaofeng Yang, Peng Wang
Timely flowering is critical for successful reproduction and seed yield in plants. A diverse range of regulators have been found to control flowering time in response to environmental and endogenous signals. Among these regulators, FLOWERING LOCUS C (FLC) acts as a central repressor of floral transition by blocking the expression of flowering integrator genes. Here, we report that Arabidopsis inositol polyphosphate multikinase (AtIPK2β) functions in flowering time control by mediating transcriptional regulation of FLC at the chromatin level...
November 17, 2017: Journal of Experimental Botany
https://www.readbyqxmd.com/read/29158814/dna-methylation-of-mir-7-is-a-mechanism-involved-in-platinum-response-through-mafg-overexpression-in-cancer-cells
#2
Olga Vera, Julia Jimenez, Olga Pernia, Carlos Rodriguez-Antolin, Carmen Rodriguez, Fatima Sanchez Cabo, Javier Soto, Rocio Rosas, Sara Lopez-Magallon, Isabel Esteban Rodriguez, Ana Dopazo, Federico Rojo, Cristobal Belda, Rafael Alvarez, Jaime Valentin, Javier Benitez, Rosario Perona, Javier De Castro, Inmaculada Ibanez de Caceres
One of the major limitations associated with platinum use is the resistance that almost invariably develops in different tumor types. In the current study, we sought to identify epigenetically regulated microRNAs as novel biomarkers of platinum resistance in lung and ovarian cancers, the ones with highest ratios of associated chemo-resistance. Methods: We combined transcriptomic data from microRNA and mRNA under the influence of an epigenetic reactivation treatment in a panel of four paired cisplatin -sensitive and -resistant cell lines, followed by real-time expression and epigenetic validations for accurate candidate selection in 19 human cancer cell lines...
2017: Theranostics
https://www.readbyqxmd.com/read/29156798/arhi-is-a-novel-epigenetic-silenced-tumor-suppressor-in-sporadic-pheochromocytoma
#3
Dong Wang, Li Song, Liang Wang, Lianmei Zhao, Bai Xiang, Ying Li, Baoen Shan, Jing Liu
Pheochromocytoma (PCC) is related to germline mutations in 12 susceptibility genes. Although comparative genomic hybridization array has revealed some putative tumor suppressor genes on the short arm of chromosome 1 that are likely to be involved in PCC tumorigenesis, the molecules involved, except for those encoded by known susceptibility genes, have not been found in the generation of sporadic tumors. In the present work, we first identified that the unmethylated allele of Aplasia Ras homolog member I (ARHI) was deleted in most PCC tumors which retained a hypermethylated copy, while its mRNA level was significantly correlated with the unmethylated copy...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29156678/epigenetic-silencing-of-tumor-suppressor-candidate-3-confers-adverse-prognosis-in-early-colorectal-cancer
#4
Elke Burgermeister, Patrick Höde, Johannes Betge, Tobias Gutting, Andreas Merkel, Wen Wu, Marc Tänzer, Maximilian Mossner, Daniel Nowak, Julia Magdeburg, Felix Rückert, Carsten Sticht, Katja Breitkopf-Heinlein, Nadine Schulte, Nicolai Härtel, Sebastian Belle, Stefan Post, Timo Gaiser, Barbara Ingold Heppner, Hans-Michael Behrens, Christoph Röcken, Matthias P A Ebert
Colorectal cancer (CRC) is a biologically and clinically heterogeneous disease. Even though many recurrent genomic alterations have been identified that may characterize distinct subgroups, their biological impact and clinical significance as prognostic indicators remain to be defined. The tumor suppressor candidate-3 (TUSC3/N33) locates to a genomic region frequently deleted or silenced in cancers. TUSC3 is a subunit of the oligosaccharyltransferase (OST) complex at the endoplasmic reticulum (ER) which catalyzes bulk N-glycosylation of membrane and secretory proteins...
October 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/29154989/targeting-bromodomain-and-extraterminal-proteins-in-breast-cancer
#5
REVIEW
Jennifer M Sahni, Ruth A Keri
Breast cancer is a collection of distinct tumor subtypes that are driven by unique gene expression profiles. These transcriptomes are controlled by various epigenetic marks that dictate which genes are expressed and suppressed. During carcinogenesis, extensive restructuring of the epigenome occurs, including aberrant acetylation, alteration of methylation patterns, and accumulation of epigenetic readers at oncogenes. As epigenetic alterations are reversible, epigenome-modulating drugs could provide a mechanism to silence numerous oncogenes simultaneously...
November 15, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/29152092/the-long-non-coding-rna-particle-is-associated-with-wwox-and-the-absence-of-fra16d-breakage-in-osteosarcoma-patients
#6
Valerie Bríd O'Leary, Doris Maugg, Jan Smida, Daniel Baumhoer, Michaela Nathrath, Saak Victor Ovsepian, Michael John Atkinson
Breakage of the fragile site FRA16D disrupts the WWOX (WW Domain Containing Oxidoreductase) tumor suppressor gene in osteosarcoma. However, the frequency of breakage is not sufficient to explain the rate of WWOX loss in pathogenesis. The involvement of non-coding RNA transcripts is proposed due to their accumulation at fragile sites, where they are advocated to influence specific chromosomal regions associated with malignancy. The long ncRNA PARTICLE (promoter of MAT2A antisense radiation-induced circulating long non-coding RNA) is transiently elevated in response to irradiation and influences epigenetic silencing modification within WWOX...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29151979/effects-of-triple-effective-rna-terna-on-the-inhibition-of-hepatocellular-carcinoma-cells
#7
Yuwen Xue, Tiejun Li, Shuyan Liu, York Yuanyuan Zhu, Guilan Wang, Luyu Fu, Li Chen
The occurrence and development of hepatocellular carcinoma (HCC) is a complicate process involved in genetic mutation and epigenetic regulation. Successful HCC therapy needs multi-targets be involved. The aim of this study was to provide a triple effective RNA (teRNA) which composed of the specific siRNAs targeting NET-1 and VEGF and dsRNA activating TLR3, and explored its anti-HCC roles and mechanism. Real-time quantitative PCR (RT-qPCR), Western blot, immunofluorescence staining, MTT, Annexin V-FITC flow cytometry, Transwell and in-vitro Angiogenesis assay were used to measure the cell biological functions and protein expression analysis...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/29145694/engineered-and-natural-promoters-and-chromatin-modifying-elements-for-recombinant-protein-expression-in-cho-cells
#8
REVIEW
Nadiya Romanova, Thomas Noll
Promoters play a pivotal role in integrating and processing the signals related to transcription initiation. Strong natural viral promoters, such as hCMV or SV40E, have been routinely employed to achieve a high rate of gene expression in ubiquitously used Chinese hamster ovary (CHO) cells. However, viral promoters are susceptible to epigenetic silencing and lack precise regulation levers. This has paved the way to more sensible control elements: endogenous, inducible and synthetic promoters. In this review we summarise and discuss the use of natural viral, mammalian and endogenous promoters, as well as recent advances in synthetic promoters and inducible systems for protein expression in CHO cells...
November 16, 2017: Biotechnology Journal
https://www.readbyqxmd.com/read/29143365/epigenetic-down-regulation-of-sox2-is-an-independent-poor-prognostic-factor-for-hypopharyngeal-cancers
#9
Mehmet Ozgur Avincsal, Naoe Jimbo, Kohei Fujikura, Hirotaka Shinomiya, Naoki Otsuki, Koichi Morimoto, Tatsuya Furukawa, Naruhiko Morita, Ritsuko Maehara, Tomoo Itoh, Ken-Ichi Nibu, Yoh Zen
AIMS: We recently reported that a small subset (7%) of oesophageal squamous cell carcinomas completely lacking SOX2 expression had unique clinicopathological features and a dismal prognosis. The present study aimed to elucidate whether the findings obtained in oesophageal cancers are applicable to hypopharyngeal or oropharyngeal squamous cell carcinomas (HPSCCs or OPSCCs, respectively). METHODS AND RESULTS: The study cohort consisted of consecutive patients with HPSCC (n=130) and OPSCC (n=65) who underwent surgery without preoperative therapy...
November 15, 2017: Histopathology
https://www.readbyqxmd.com/read/29143120/epigenetic-silencing-of-adamts5-is-associated-with-increased-invasiveness-and-poor-survival-in-patients-with-colorectal-cancer
#10
Jizhen Li, Yi Liao, Jintuan Huang, Yi Sun, Hao Chen, Chunyu Chen, Senmao Li, Zuli Yang
A disintegrin and metalloprotease with motif 5(ADAMTS5) has been involved in colorectal cancer (CRC) with hypermethylation in the promoter. However, its role in CRC remains unclear. The aim of this study was to explore the clinical significance and biological effect of ADAMTS5 on colorectal carcinogenesis. Through MSP, qRT-PCR, WB and IHC analysis, followed by a variety of in vitro assays, we report the function of ADAMTS5 in CRC. ADAMTS5 was markedly hypermethylaed and downregulated in tumor tissues compared with non-tumor tissues (p < 0...
November 15, 2017: Journal of Cancer Research and Clinical Oncology
https://www.readbyqxmd.com/read/29140109/host-methyltransferases-and-demethylases-potential-new-epigenetic-targets-for-hiv-cure-strategies-and-beyond
#11
Daniela Boehm, Melanie Ott
A successful HIV cure strategy may require reversing HIV latency to purge hidden viral reservoirs or enhancing HIV latency to permanently silence HIV transcription. Epigenetic modifying agents show promise as antilatency therapeutics in vitro and ex vivo, but also affect other steps in the viral life cycle. In this review, we summarize what we know about cellular DNA and protein methyltransferases (PMTs) as well as demethylases involved in HIV infection. We describe the biology and function of DNA methyltransferases, and their controversial role in HIV infection...
November 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/29139562/lncrna-ghet1-predicts-poor-prognosis-in-hepatocellular-carcinoma-and-promotes-cell-proliferation-by-silencing-klf2
#12
Li Jin, Yangke He, Shijia Tang, Shan Huang
BACKGROUND: Hepatocellular carcinoma (HCC) has been identified as one of the leading causes of cancer-related death worldwide. Recently, long non-coding RNAs (lncRNAs) attract much attention of researchers, and they are demonstrated to be dysregulated in a variety of cancers, including HCC. LncRNA gastric carcinoma high expressed transcript 1 lncRNA GHET1 is found to be dysregulated in gastric cancer (GC). However, its clinical value and potential biological function in HCC remains unclear...
November 15, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/29137437/dna-hypermethyation-and-silencing-of-pitx1-correlated-with-advanced-stage-and-poor-postoperative-prognosis-of-esophageal-squamous-cell-carcinoma
#13
Takeshi Otsubo, Kazuhiko Yamada, Teruki Hagiwara, Kenshiro Oshima, Kei Iida, Koro Nishikata, Tetsuro Toyoda, Toru Igari, Kyoko Nohara, Satoshi Yamashita, Masahira Hattori, Taeko Dohi, Yuki I Kawamura
Esophageal squamous cell carcinoma (ESCC) is associated with the accumulation of genetic and epigenetic changes in the background mucosa. Dysregulated DNA methylation is known to lead to the inactivation of tumor suppressor genes and the activation of oncogenes. To identify the genes whose expression is perturbed by abnormal DNA methylation in ESCC, integrative transcriptomics by serial analysis of gene expression (SAGE) and methylome sequencing by methyl-DNA immunoprecipitation (MeDIP) analysis were performed...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137417/inhibition-of-retinoic-acid-receptor-%C3%AE-signaling-confers-glycolytic-dependence-and-sensitization-to-dichloroacetate-in-melanoma-cells
#14
Cecilie Abildgaard, Christina Dahl, Ahmad Abdul-Al, Annette Christensen, Per Guldberg
Dysregulation of metabolism during melanoma progression is tightly associated with the acquisition of genetic and epigenetic alterations in regulators of metabolic pathways. Retinoic acid receptor beta (RARβ) is epigenetically silenced in a large proportion of melanomas, but a link between RARβ and metabolic rewiring of melanoma has not been established. Here, we show that in primary human melanocytes, all-trans retinoic acid (a RARβ agonist) induced growth inhibition accompanied by a decrease in both glycolytic and oxidative metabolism, whereas selective inhibition of RARβ led to an increase in the basal glycolytic rate and increased sensitivity to inhibition of glycolysis...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137219/functional-characterization-of-lysine-specific-demethylase-2-lsd2-kdm1b-in-breast-cancer-progression
#15
Lin Chen, Shauna N Vasilatos, Ye Qin, Tiffany A Katz, Chunyu Cao, Hao Wu, Nilgun Tasdemir, Kevin M Levine, Steffi Oesterreich, Nancy E Davidson, Yi Huang
Flavin-dependent histone demethylases govern histone H3K4 methylation and act as important chromatin modulators that are extensively involved in regulation of DNA replication, gene transcription, DNA repair, and heterochromatin gene silencing. While the activities of lysine-specific demethylase 1 (LSD1/KDM1A) in facilitating breast cancer progression have been well characterized, the roles of its homolog LSD2 (KDM1B) in breast oncogenesis are relatively less understood. In this study, we showed that LSD2 protein level was significantly elevated in malignant breast cell lines compared with normal breast epithelial cell line...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29130960/piwi-proteins-and-piwi-interacting-rna-emerging-roles-in-cancer
#16
Yi-Neng Han, Yuan Li, Sheng-Qiang Xia, Yuan-Yuan Zhang, Jun-Hua Zheng, Wei Li
P-Element induced wimpy testis (PIWI)-interacting RNAs (piRNAs) are a type of noncoding RNAs (ncRNAs) and interact with PIWI proteins. piRNAs were primarily described in the germline, but emerging evidence revealed that piRNAs are expressed in a tissue-specific manner among multiple human somatic tissue types as well and play important roles in transposon silencing, epigenetic regulation, gene and protein regulation, genome rearrangement, spermatogenesis and germ stem-cell maintenance. PIWI proteins were first discovered in Drosophila and they play roles in spermatogenesis, germline stem-cell maintenance, self-renewal, retrotransposons silencing and the male germline mobility control...
November 3, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29128342/readers-of-dna-methylation-the-mbd-family-as-potential-therapeutic-targets
#17
REVIEW
Gordon D Ginder, David C Williams
DNA methylation represents a fundamental epigenetic modification that regulates chromatin architecture and gene transcription. Many diseases, including cancer, show aberrant methylation patterns that contribute to the disease phenotype. DNA methylation inhibitors have been used to block methylation dependent gene silencing to treat hematopoietic neoplasms and to restore expression of developmentally silenced genes. However, these inhibitors disrupt methylation globally and show significant off-target toxicities...
November 8, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/29127737/genomic-data-from-arthropods-reveal-high-conservation-but-divergent-evolutionary-pattern-of-polycomb-trithorax-group-genes-in-arthropods
#18
Feng Jiang, Qing Liu, Xiang Liu, Xian-Hui Wang, Le Kang
Epigenetic gene control is maintained by chromatin-associated Polycomb group (PcG) and Trithorax group (TrxG) genes, which act antagonistically via the interplay between PcG and TrxG regulation to generate silenced or permissive transcriptional states. In this study, we searched for PcG/TrxG genes in 180 arthropod genomes, covering all the sequenced arthropod genomes at the time of conducting this study, to perform a global investigation of PcG/TrxG genes in a phylogenetic frame. Results of ancestral state reconstruction analysis revealed that the ancestor of arthropod species has an almost complete repertoire of PcG/TrxG genes, and most of these genes were seldom lost above order level...
November 11, 2017: Insect Science
https://www.readbyqxmd.com/read/29126199/evolutionary-epigenomics-of-retrotransposon-mediated-methylation-spreading-in-rice-by
#19
Jae Young Choi, Michael D Purugganan
Plant genomes contain numerous transposable elements (TEs), and many hypotheses on the evolutionary drivers that restrict TE activity have been postulated. Few models, however, have focused on the evolutionary epigenomic interaction between the plant host and its TE. The host genome recruits epigenetic factors, such as methylation, to silence TEs but methylation can spread beyond the TE sequence and influence the expression of nearby host genes. In this study, we investigated this epigenetic trade-off between TE and proximal host gene silencing by studying the epigenomic regulation of repressing long terminal repeat (LTR) retrotransposons (RTs) in Oryza sativa...
November 6, 2017: Molecular Biology and Evolution
https://www.readbyqxmd.com/read/29124315/the-class-i-iv-hdac-inhibitor-mocetinostat-increases-tumor-antigen-presentation-decreases-immune-suppressive-cell-types-and-augments-checkpoint-inhibitor-therapy
#20
David Briere, Niranjan Sudhakar, David M Woods, Jill Hallin, Lars D Engstrom, Ruth Aranda, Harrah Chiang, Andressa L Sodré, Peter Olson, Jeffrey S Weber, James G Christensen
Checkpoint inhibitor therapy has led to major treatment advances for several cancers including non-small cell lung cancer (NSCLC). Despite this, a significant percentage of patients do not respond or develop resistance. Potential mechanisms of resistance include lack of expression of programmed death ligand 1 (PD-L1), decreased capacity to present tumor antigens, and the presence of an immunosuppressive tumor microenvironment. Mocetinostat is a spectrum-selective inhibitor of class I/IV histone deacetylases (HDACs), a family of proteins implicated in epigenetic silencing of immune regulatory genes in tumor and immune cells...
November 9, 2017: Cancer Immunology, Immunotherapy: CII
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