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Telomere and telomerase

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https://www.readbyqxmd.com/read/28943954/epigallocatechin-3-gallate-suppresses-cell-proliferation-and-promotes-apoptosis-in-ec9706-and-eca109-esophageal-carcinoma-cells
#1
Liang Liu, Jing Zuo, Guangda Wang
Epigallocatechin-3-gallate (EGCG) is a component of green tea with anticancer effects that have been demonstrated in multiple types of cancer, but few reports exist concerning its effect in esophageal squamous cell carcinoma cells. The present study investigated apoptosis induced by EGCG treatment and the underlying molecular mechanisms in Eca109 and Ec9706 human esophageal squamous cell carcinoma cells. The apoptosis rate following treatment with various concentration of EGCG for 24 h was detected by flow cytometry...
October 2017: Oncology Letters
https://www.readbyqxmd.com/read/28942425/chromosome-healing-is-promoted-by-the-telomere-cap-component-hiphop-in-drosophila
#2
Rebeccah L Kurzhals, Laura Fanti, A C Gonzalez Ebsen, Yikang S Rong, Sergio Pimpinelli, Kent G Golic
The addition of a new telomere onto a chromosome break, a process termed healing, has been studied extensively in organisms that utilize telomerase to maintain their telomeres. In comparison, relatively little is known about how new telomeres are constructed on broken chromosomes in organisms that do not use telomerase. Chromosome healing was studied in somatic and germline cells of Drosophila melanogaster, a non-telomerase species. We observed, for the first time, that broken chromosomes can be healed in somatic cells...
September 23, 2017: Genetics
https://www.readbyqxmd.com/read/28928745/chronic-inflammation-in-immune-aging-role-of-pattern-recognition-receptor-crosstalk-with-the-telomere-complex
#3
REVIEW
Shyam Sushama Jose, Kamila Bendickova, Tomas Kepak, Zdenka Krenova, Jan Fric
Age-related decline in immunity is characterized by stem cell exhaustion, telomere shortening, and disruption of cell-to-cell communication, leading to increased patient risk of disease. Recent data have demonstrated that chronic inflammation exerts a strong influence on immune aging and is closely correlated with telomere length in a range of major pathologies. The current review discusses the impact of inflammation on immune aging, the likely molecular mediators of this process, and the various disease states that have been linked with immunosenescence...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28927529/targeting-telomerase-and-telomeres-to-enhance-ionizing-radiation-effects-in-in-vitro-and-in-vivo-cancer-models
#4
REVIEW
F Berardinelli, E Coluzzi, A Sgura, A Antoccia
One of the hallmarks of cancer consists in the ability of tumor cells to divide indefinitely, and to maintain stable telomere lengths throughout the activation of specific telomere maintenance mechanisms (TMM). Therefore in the last fifteen years, researchers proposed to target telomerase or telomeric structure in order to block limitless replicative potential of cancer cells providing a fascinating strategy for a broad-spectrum cancer therapy. In the present review, we report in vitro and in vivo evidence regarding the use of chemical agents targeting both telomerase or telomere structure and showing promising antitumor effects when used in combination with ionizing radiation (IR)...
July 2017: Mutation Research
https://www.readbyqxmd.com/read/28900814/sub-fertile-sperm-cells-exemplify-telomere-dysfunction
#5
Tal Biron-Shental, Amir Wiser, Anat Hershko-Klement, Ofer Markovitch, Aliza Amiel, Arie Berkovitch
PURPOSE: The purpose of this study was to evaluate telomere homeostasis in sub-fertile compared to fertile human sperm. METHODS: This observational, comparative study included 16 sub-fertile men who required intracytoplasmic sperm injection and 10 fertile men. At least 100 sperm cells from each participant were assessed. Main outcome measures were telomere length and telomere aggregates. Telomerase RNA component (TERC) copy number and telomere capture were assessed using fluorescence in situ hybridization technique and human telomerase reverse transcriptase (hTERT) using immunohistochemistry...
September 13, 2017: Journal of Assisted Reproduction and Genetics
https://www.readbyqxmd.com/read/28895292/pathology-and-genomics-of-pediatric-melanoma-a-critical-reexamination-and-new-insights
#6
REVIEW
Armita Bahrami, Raymond L Barnhill
The clinicopathologic features of pediatric melanoma are distinct from those of the adult counterpart. For example, most childhood melanomas exhibit a uniquely favorable biologic behavior, save for those arising in large/giant congenital nevi. Recent studies suggest that the characteristically favorable biologic behavior of childhood melanoma may be related to extreme telomere shortening and dysfunction in the cancer cells. Herein, we review the genomic profiles that have been defined for the different subtypes of pediatric melanoma and particularly emphasize the potential prognostic value of telomerase reverse transcriptase alterations for these tumors...
September 12, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28893481/telomerase-based-anticancer-immunotherapy-and-vaccines-approaches
#7
REVIEW
Chahal Kailashiya, Hanjabam Barun Sharma, Jyotsna Kailashiya
Telomerase is a Reverse Transcriptase that maintains the telomere length. It is absent in most somatic cells but is found in stem cells, germ cells and around 90% of cancers. It plays a crucial role in developing and maintaining cancer cells. Telomerase, a HLA class-I antigen, is able to stimulate cell mediated immune response by inducing cytotoxic T-cells. This property of telomerase is being exploited in targeting cancers by host's own immune responses; stimulated by various Human Telomerase Reverse Transcriptase (hTERT) derived vaccines...
September 8, 2017: Vaccine
https://www.readbyqxmd.com/read/28889732/effects-of-water-extract-of-curcuma-longa-l-roots-on-immunity-and-telomerase-function
#8
Min-Hsiung Pan, Jia-Ching Wu, Chi-Tang Ho, Vladimir Badmaev
Background Immunity and Longevity Methods A water extract of Curcuma longa (L.) [vern. Turmeric] roots (TurmericImmune™) standardized for a minimum 20 % of turmeric polysaccharides ukonan A, B, C and D was evaluated for its biological properties in in vitro tissue culture studies. Results The water extract of turmeric (TurP) exhibited induced-nitric oxide (NO) production in RAW264.7 macrophages. These results suggested the immunomodulatory effects of TurP. In addition, the polysaccharides up-regulated function of telomerase reverse transcriptase (TERT) equally to the phenolic compound from turmeric, curcumin...
May 12, 2017: Journal of Complementary & Integrative Medicine
https://www.readbyqxmd.com/read/28888820/design-and-synthesis-of-2-phenylpyrimidine-coumarin-derivatives-as-anticancer-agents
#9
Na Lv, Ming Sun, Chen Liu, Jiabin Li
A series of 2-phenylpyrimidine coumarin derivatives with potential telomerase-inhibiting activity was designed and synthesized. All of the compounds were screened for antiproliferative activity against CNE2, KB, and Cal27 cell lines in vitro. The results showed that most of the derivatives had a favorable effect on resisting tumor cell proliferation; compound 13, 3-(4-amino-5-oxo-5H-chromeno[4,3-d]pyrimidin-2-yl)phenyl 4-(dimethylamino)benzenesulfonate, exhibited the best activity. Flow cytometry revealed that compound 13 can inhibit CNE2 proliferation...
August 24, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28888037/myc-drives-overexpression-of-telomerase-rna-htr-terc-in-prostate-cancer
#10
Javier A Baena-Del Valle, Qizhi Zheng, David M Esopi, Michael Rubenstein, Gretchen K Hubbard, Maria C Moncaliano, Andrew Hruszkewycz, Ajay Vaghasia, Srinivasan Yegnasubramanian, Sarah J Wheelan, Alan K Meeker, Christopher M Heaphy, Mindy K Graham, Angelo M De Marzo
Telomerase consists of at least two essential elements, an RNA component hTR or TERC that contains the template for telomere DNA addition, and a catalytic reverse transcriptase (TERT). While expression of TERT has been considered the key rate limiting component for telomerase activity, increasing evidence suggests an important role for the regulation of TERC in telomere maintenance and perhaps other functions in human cancer. By using three orthogonal methods including RNAseq, RT-qPCR, and an analytically validated chromogenic RNA in situ hybridization assay, we report consistent overexpression of TERC in prostate cancer...
September 9, 2017: Journal of Pathology
https://www.readbyqxmd.com/read/28887594/do-long-telomeres-affect-cellular-fitness
#11
REVIEW
Yaniv Harari, Martin Kupiec
Telomeres protect the chromosome ends and maintain the genome stability; they, therefore, play important roles in aging and cancer. Despite the wide variability in telomere length among eukaryotes, in all telomerase-expressing cells telomere length is strictly controlled within a very narrow range. In humans, telomeres shorten with age, and it has been proposed that telomere shortening may play a causal role in aging. Using yeast strains with genetically or physiologically generated differences in telomere length, we have explored the question of whether having long telomeres affects telomere function and fitness or cellular lifespan...
September 8, 2017: Current Genetics
https://www.readbyqxmd.com/read/28886883/alternative-splicing-of-telomerase-catalytic-subunit-htert-generated-by-apoptotic-endonuclease-endog-induces-human-cd4-t-cell-death
#12
Dmitry D Zhdanov, Daria A Vasina, Vladimir A Grachev, Elena V Orlova, Valentina S Orlova, Marina V Pokrovskaya, Svetlana S Alexandrova, Nikolai N Sokolov
Telomerase activity is regulated by alternative splicing of its catalytic subunit human Telomerase Reverse Transcriptase (hTERT) mRNA. Induction of a non-active spliced hTERT leads to inhibition of telomerase activity. However, very little is known about the mechanism of hTERT mRNA alternative splicing. The aim of this study was to determine the role of the apoptotic endonuclease EndoG in alternative splicing of hTERT and telomerase activity. A strong correlation was identified between EndoG expression levels and hTERT splice variants in human CD4(+) and CD8(+) T lymphocytes...
September 1, 2017: European Journal of Cell Biology
https://www.readbyqxmd.com/read/28855418/analyses-of-selenotranscriptomes-and-selenium-concentrations-in-response-to-dietary-selenium-deficiency-and-age-reveal-common-and-distinct-patterns-by-tissue-and-sex-in-telomere-dysfunctional-mice
#13
Lei Cao, Li Zhang, Huawei Zeng, Ryan Ty Wu, Tung-Lung Wu, Wen-Hsing Cheng
Background: The hierarchies of tissue selenium distribution and selenotranscriptomes are thought to critically affect healthspan and longevity.Objective: We determined selenium status and selenotranscriptomes in response to long-term dietary selenium deficiency and age in tissues of male and female mice.Methods: Weanling telomerase RNA component knockout C57BL/6 mice were fed a selenium-deficient (0.03 mg Se/kg) Torula yeast-based AIN-93G diet or a diet supplemented with sodium selenate (0.15 mg Se/kg) until age 18 or 24 mo...
August 30, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28854735/brd4-inhibitors-block-telomere-elongation
#14
Steven Wang, Alexandra M Pike, Stella S Lee, Margaret A Strong, Carla J Connelly, Carol W Greider
Cancer cells maintain telomere length equilibrium to avoid senescence and apoptosis induced by short telomeres, which trigger the DNA damage response. Limiting the potential for telomere maintenance in cancer cells has been long been proposed as a therapeutic target. Using an unbiased shRNA screen targeting known kinases, we identified bromodomain-containing protein 4 (BRD4) as a telomere length regulator. Four independent BRD4 inhibitors blocked telomere elongation, in a dose-dependent manner, in mouse cells overexpressing telomerase...
August 21, 2017: Nucleic Acids Research
https://www.readbyqxmd.com/read/28854689/identification-and-characterization-of-a-subtelomeric-satellite-dna-in-callitrichini-monkeys
#15
Naiara Pereira Araújo, Leonardo Gomes de Lima, Guilherme Borges Dias, Gustavo Campos Silva Kuhn, Alan Lane de Melo, Yatiyo Yonenaga-Yassuda, Roscoe Stanyon, Marta Svartman
Repetitive DNAs are abundant fast-evolving components of eukaryotic genomes, which often possess important structural and functional roles. Despite their ubiquity, repetitive DNAs are poorly studied when compared with the genic fraction of genomes. Here, we took advantage of the availability of the sequenced genome of the common marmoset Callithrix jacchus to assess its satellite DNAs (satDNAs) and their distribution in Callitrichini. After clustering analysis of all reads and comparisons by similarity, we identified a satDNA composed by 171 bp motifs, named MarmoSAT, which composes 1...
August 1, 2017: DNA Research: An International Journal for Rapid Publication of Reports on Genes and Genomes
https://www.readbyqxmd.com/read/28843010/telomerase-activity-telomere-length-and-htert-dna-methylation-in-peripheral-blood-mononuclear-cells-from-monozygotic-twins-with-discordant-smoking-habits
#16
Francesca Marcon, Ester Siniscalchi, Cristina Andreoli, Alessandra Allione, Giovanni Fiorito, Emanuela Medda, Simonetta Guarrera, Giuseppe Matullo, Riccardo Crebelli
Increased telomerase expression has been implicated in the pathogenesis of lung cancer and, since the primary cause of lung cancer is smoking, an association between telomerase reactivation and tobacco smoke has been proposed. In this work an investigation has been performed to assess the relationship between tobacco smoke exposure and telomerase activity (TA) in peripheral blood mononuclear cells of healthy smokers. The methylation status of the catalytic subunit of telomerase hTERT was concurrently investigated to assess the possible association between epigenetic modifications of hTERT and TA...
August 26, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28839469/rbfox3-promotes-tumor-growth-and-progression-via-htert-signaling-and-predicts-a-poor-prognosis-in-hepatocellular-carcinoma
#17
Tianze Liu, Wenbin Li, Wenjing Lu, Miao Chen, Meihua Luo, Changlin Zhang, Yixin Li, Ge Qin, Dingbo Shi, Binyi Xiao, Huijuan Qiu, Wendan Yu, Lan Kang, Tiebang Kang, Wenlin Huang, Xinfa Yu, Xiaojun Wu, Wuguo Deng
Activation of the telomere maintenance mechanism is a key hallmark of cancer. Human telomerase reverse transcriptase (hTERT) is the catalytic subunit of telomerase, which is highly expressed in more than 80% of tumors, including hepatocellular carcinoma (HCC). However, the exact mechanisms by which hTERT is up-regulated in HCCs and promotes tumor growth and progression is not fully understood. The aim of this study was to discover the novel molecular targets that modulate hTERT signaling and HCC growth. In this study, we pulled down and identified RBFOX3 (RNA binding protein fox-1 homolog 3) as a novel hTERT promoter-binding protein in HCC cells using biotin-streptavidin-agarose pull-down and proteomics approach, and validated it as a regulatory factor for hTERT signaling and tumor growth in HCCs...
2017: Theranostics
https://www.readbyqxmd.com/read/28837806/rhodospirillum-rubruml-asparaginase-targets-tumor-growth-by-a-dual-mechanism-involving-telomerase-inhibition
#18
Dmitry D Zhdanov, Vadim S Pokrovsky, Marina V Pokrovskaya, Svetlana S Alexandrova, Mikhail A Eldarov, Dmitry V Grishin, Marsel M Basharov, Yulia A Gladilina, Olga V Podobed, Nikolai N Sokolov
Rhodospirillum rubruml-asparaginase mutant RrA E149R, V150P, F151T (RrA) was previously identified to down-regulate telomerase activity along with catalyzing the hydrolysis of l-asparagine. The aim of this study was to define the effect of prolonged RrA exposure on telomerase activity, maintenance of telomeres and proliferation of cancer cells in vitro and in vivo. RrA could inhibit telomerase activity in SCOV-3, SkBr-3 and A549 human cancer cell lines due to its ability to down-regulate the expression of telomerase catalytic subunit hTERT...
October 14, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28833505/aberrant-levels-of-suv39h1-and-suv39h2-methyltransferase-are-associated-with-genomic-instability-in-chronic-lymphocytic-leukemia
#19
Juliana Carvalho Alves-Silva, Doralina do Amaral Rabello, Martha Oliveira Bravo, Antônio Roberto Lucena-Araujo, Diego Madureira de Oliveira, Fábio Morato de Oliveira, Eduardo Magalhaes Rego, Fábio Pittella-Silva, Felipe Saldanha-Araujo
Chromosomal alterations are commonly detected in patients with chronic lymphocytic leukemia (CLL) and impact disease pathogenesis, prognosis, and progression. Telomerase expression (hTERT), its activity and the telomere length are other important predictors of survival and multiple outcomes in CLL. SUV39H and SUV420H enzymes are histone methyltransferases (HMTases) involved in several cellular processes, including regulation of telomere length, heterochromatin organization, and genome stability. Here, we investigated whether SUV39H1, SUV39H2, SUV420H1, SUV420H2, and hTERT are associated with genomic instability of CLL...
August 19, 2017: Environmental and Molecular Mutagenesis
https://www.readbyqxmd.com/read/28833123/telomere-length-variation-in-tumor-cells-and-cancer-associated-fibroblasts-potential-biomarker-for-hepatocellular-carcinoma
#20
Li-Jie Ma, Xiao-Ying Wang, Meng Duan, Long-Zi Liu, Jie-Yi Shi, Liang-Qing Dong, Liu-Xiao Yang, Zhi-Chao Wang, Zhen-Bin Ding, Ai-Wu Ke, Ya Cao, Xiao-Ming Zhang, Jian Zhou, Jia Fan, Qiang Gao
The role of telomere dysfunction and aberrant telomerase activities in hepatocellular carcinoma (HCC) has been overlooked for many years. This study aimed to delineate the variation and prognostic value of telomere length in HCC. Telomere-specific fluorescence in situ hybridization (FISH) and qPCR were used to evaluate telomere length in HCC cell lines, tumor tissues and isolated non-tumor cells within the tumor. Significant telomere attrition was found in tumor cells and cancer-associated fibroblasts (CAFs) compared to their normal counterparts, but not in intratumor leukocytes or bile duct epithelial cells...
August 21, 2017: Journal of Pathology
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