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Epigenetic silencing

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https://www.readbyqxmd.com/read/29145694/engineered-and-natural-promoters-and-chromatin-modifying-elements-for-recombinant-protein-expression-in-cho-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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
#9
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
#10
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
#11
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
#12
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
#13
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
https://www.readbyqxmd.com/read/29124072/decitabine-induced-changes-in-human-myelodysplastic-syndrome-cell-line-skm-1-are-mediated-by-foxo3a-activation
#14
Wen Zeng, Hanjun Dai, Ming Yan, Xiaojun Cai, Hong Luo, Min Ke, Zeming Liu
The epigenetic silencing of tumor suppressor genes in myelodysplastic syndromes (MDS) can potentially confer a growth advantage to individual cellular clones. Currently, the recommended treatment for patients with high-risk MDS is the methylation agent decitabine (DAC), a drug that can induce the reexpression of silenced tumor suppressor genes. We investigated the effects of DAC treatment on the myeloid MDS cell line SKM-1 and investigated the role of FOXO3A, a potentially tumor-suppressive transcription factor, by silencing its expression prior to DAC treatment...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/29123662/chronic-postsurgical-pain-is-there-a-possible-genetic-link
#15
Sabu Kumar James
Persistent or chronic postsurgical pain (CPSP) has been defined as 'pain persisting beyond 2 months'. The cut-off limit of 2 months has been controversial, and some researchers argue for a 3-month period for the definition of CPSP. Multiple mechanisms, including both patient and surgical, have been shown to influence this transition. Patient factors include age, gender, anxiety, depression, somatisation, catastrophising, pre-existing pain anywhere and pain at the site of surgery. The various surgical factors include site and nature of surgery, infection, inflammation and repeat surgery...
November 2017: British Journal of Pain
https://www.readbyqxmd.com/read/29121502/the-prognostic-role-of-epigenetic-dysregulation-in-bladder-cancer-a-systematic-review
#16
REVIEW
David Casadevall, Anaïs Yacine Kilian, Joaquim Bellmunt
BACKGROUND: Despite adequate treatment and follow-up, around one fifth of patients with localized bladder cancer will present with disease progression. Adequate prognostic biomarkers are lacking to define patients who are at risk. Mutations in chromatin remodeling genes are more frequently found in bladder cancer than in any other solid tumor. However, the prognostic relevance of epigenetic dysregulation has not been established and may offer an opportunity for biomarker discovery. METHODS: Looking for prognostic epigenetic factors, we performed a comprehensive PubMed search using keywords such as "bladder cancer", "chromatin remodeling", "gene methylation" and "epigenetics"...
November 6, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/29120412/bortezomib-induced-mirnas-direct-epigenetic-silencing-of-locus-genes-and-trigger-apoptosis-in-leukemia
#17
Yu-Yi Chu, Chiung-Yuan Ko, Shao-Ming Wang, Pin-I Lin, Han-Ying Wang, Wen-Chi Lin, Dong-Yu Wu, Lu-Hao Wang, Ju-Ming Wang
MicroRNAs (miRNAs) have been suggested to repress transcription via binding the 3'-untranslated regions of mRNAs. However, the involvement and details of miRNA-mediated epigenetic regulation, particularly in targeting genomic DNA and mediating epigenetic regulation, remain largely uninvestigated. In the present study, transcription factor CCAAT/enhancer binding protein delta (CEBPD) was responsive to the anticancer drug bortezomib, a clinical and highly selective drug for leukemia treatment, and contributed to bortezomib-induced cell death...
November 9, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29119846/carbonate-apatite-nanoparticles-carry-sirna-s-targeting-growth-factor-receptor-genes-egfr1-and-erbb2-to-regress-mouse-breast-tumor
#18
Snigdha Tiash, Nur Izyani Binti Kamaruzman, Ezharul Hoque Chowdhury
Cancer cells lose their control on cell cycle by numerous genetic and epigenetic alterations. In a tumor, these cells highly express growth factor receptors (GFRs), eliciting growth, and cell division. Among the GFRs, epidermal growth factor receptor-1 (EGFR1) (Her1/ERBB1) and epidermal growth factor receptor-2 (EGFR2) (Her2/ERBB2) from epidermal growth factor (EGF) family and insulin-like growth factor-1 receptor (IGF1R) are highly expressed on breast cancer cells, thus contributing to the aggressive growth and invasiveness, have been focused in this study...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/29119601/an-integrative-approach-to-assess-x-chromosome-inactivation-using-allele-specific-expression-with-applications-to-epithelial-ovarian-cancer
#19
Nicholas B Larson, Zachary C Fogarty, Melissa C Larson, Kimberly R Kalli, Kate Lawrenson, Simon Gayther, Brooke L Fridley, Ellen L Goode, Stacey J Winham
X-chromosome inactivation (XCI) epigenetically silences transcription of an X chromosome in females; patterns of XCI are thought to be aberrant in women's cancers, but are understudied due to statistical challenges. We develop a two-stage statistical framework to assess skewed XCI and evaluate gene-level patterns of XCI for an individual sample by integration of RNA sequence, copy number alteration, and genotype data. Our method relies on allele-specific expression (ASE) to directly measure XCI and does not rely on male samples or paired normal tissue for comparison...
November 8, 2017: Genetic Epidemiology
https://www.readbyqxmd.com/read/29118343/exosc10-rrp6-is-post-translationally-regulated-in-male-germ-cells-and-controls-the-onset-of-spermatogenesis
#20
Soazik P Jamin, Fabrice G Petit, Christine Kervarrec, Fatima Smagulova, Doris Illner, Harry Scherthan, Michael Primig
EXOSC10 is a catalytic subunit of the exosome that processes biologically active transcripts, degrades aberrant mRNAs and targets certain long non-coding RNAs (lncRNAs). The yeast orthologue Rrp6 is required for efficient growth and gametogenesis, and becomes unstable during meiosis. However, nothing is known about the localization, stability and function of EXOSC10 in the rodent male germline. We detect the protein in nucleoli and the cytoplasm of mitotic and meiotic germ cells, and find that it transiently associates with the XY body, a structure targeted by meiotic sex chromosome inactivation (MSCI)...
November 8, 2017: Scientific Reports
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