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Telomere reverse transcriptase

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https://www.readbyqxmd.com/read/28900814/sub-fertile-sperm-cells-exemplify-telomere-dysfunction
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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/28886883/alternative-splicing-of-telomerase-catalytic-subunit-htert-generated-by-apoptotic-endonuclease-endog-induces-human-cd4-t-cell-death
#7
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/28839469/rbfox3-promotes-tumor-growth-and-progression-via-htert-signaling-and-predicts-a-poor-prognosis-in-hepatocellular-carcinoma
#8
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/28833123/telomere-length-variation-in-tumor-cells-and-cancer-associated-fibroblasts-potential-biomarker-for-hepatocellular-carcinoma
#9
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
https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#10
Flávia S Donaires, Natália F Scatena, Raquel M Alves-Paiva, Joshua D Podlevsky, Dhenugen Logeswaran, Barbara A Santana, Andreza C Teixeira, Julian J-L Chen, Rodrigo T Calado, Ana L C Martinelli
Telomeres are repetitive DNA sequences at linear chromosome termini, protecting chromosomes against end-to-end fusion and damage, providing chromosomal stability. Telomeres shorten with mitotic cellular division, but are maintained in cells with high proliferative capacity by telomerase. Loss-of-function mutations in telomere-maintenance genes are genetic risk factors for cirrhosis development in humans and murine models. Telomerase deficiency provokes accelerated telomere shortening and dysfunction, facilitating genomic instability and oncogenesis...
2017: PloS One
https://www.readbyqxmd.com/read/28765565/telomerase-reverse-transcriptase-promotes-chemoresistance-by-suppressing-cisplatin-dependent-apoptosis-in-osteosarcoma-cells
#11
Zhengpei Zhang, Ling Yu, Guo Dai, Kezhou Xia, Gaiwei Liu, Qi Song, Chunjie Tao, Tian Gao, Weichun Guo
Cisplatin is one of the most efficacious antimitotic drugs used in the treatment of a range of malignant tumors. However, treatment failures are common due to the development of chemoresistance. In addition to its telomere maintenance function, telomerase plays a pro-survival role, inducing decreased apoptosis and increased resistance against DNA damage. Elucidation of the molecular mechanisms underlying this effect is critical to improve treatment outcomes. Previously, our group showed higher telomerase reverse transcriptase(TERT) expression in cisplatin resistant osteosarcoma cells...
August 1, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28732250/structural-biology-of-telomerase-and-its-interaction-at-telomeres
#12
REVIEW
Yaqiang Wang, Juli Feigon
Telomerase is an RNP that synthesizes the 3' ends of linear chromosomes and is an important regulator of telomere length. It contains a single long non-coding telomerase RNA (TER), telomerase reverse transcriptase (TERT), and other proteins that vary among organisms. Recent progress in structural biology of telomerase includes reports of the first cryo-electron microscopy structure of telomerase, from Tetrahymena, new crystal structures of TERT domains, telomerase RNA structures and models, and identification in Tetrahymena telomerase holoenzyme of human homologues of telomere-associated proteins that have provided a more unified view of telomerase interaction at telomeres as well as insights into the role of telomerase RNA in activity and assembly...
July 18, 2017: Current Opinion in Structural Biology
https://www.readbyqxmd.com/read/28704482/proteomic-identification-of-proteins-differentially-expressed-following-overexpression-of-htert-human-telomerase-reverse-transcriptase-in-cancer-cells
#13
Rishi Kumar Jaiswal, Pramod Kumar, Amod Sharma, Deepak Kumar Mishra, Pramod Kumar Yadava
Reverse transcriptase activity of telomerase adds telomeric repeat sequences at extreme ends of the newly replicated chromosome in actively dividing cells. Telomerase expression is not detected in terminally differentiated cells but is noticeable in 90% of the cancer cells. hTERT (human telomerase reverse transcriptase) expression seems to promote invasiveness of cancer cells. We here present proteomic profiles of cells overexpressing or knocked down for hTERT. This study also attempts to find out the potential interacting partners of hTERT in cancer cell lines...
2017: PloS One
https://www.readbyqxmd.com/read/28700015/telomere-length-and-htert-in-mania-and-subsequent-remission
#14
Rugül Köse Çinar
Objective: The findings of telomere length (TL) studies in bipolar disorder (BD) are controversial. The aim of the present study was to detect TL, human telomerase reverse transcriptase (hTERT), and brain derived neurotrophic factor (BDNF) in severe mania and subsequent remission. Methods: Twenty-one medication-free male patients and 20 age and gender matched controls were recruited. The patients were followed in the inpatient clinic, and comparisons were made between the same patients in their remission state and controls...
July 6, 2017: Revista Brasileira de Psiquiatria
https://www.readbyqxmd.com/read/28697848/roles-of-rnase-p-and-its-subunits
#15
REVIEW
Nayef Jarrous
Recent studies show that nuclear RNase P is linked to chromatin structure and function. Thus, variants of this ribonucleoprotein (RNP) complex bind to chromatin of small noncoding RNA genes; integrate into initiation complexes of RNA polymerase (Pol) III; repress histone H3.3 nucleosome deposition; control tRNA and PIWI-interacting RNA (piRNA) gene clusters for genome defense; and respond to Werner syndrome helicase (WRN)-related replication stress and DNA double-strand breaks (DSBs). Likewise, the related RNase MRP and RMRP-TERT (telomerase reverse transcriptase) are implicated in RNA-dependent RNA polymerization for chromatin silencing, whereas the telomerase carries out RNA-dependent DNA polymerization for telomere lengthening...
July 8, 2017: Trends in Genetics: TIG
https://www.readbyqxmd.com/read/28677271/telomerase-reverse-transcriptase-germline-mutations-and-hepatocellular-carcinoma-in-patients-with-nonalcoholic-fatty-liver-disease
#16
Benedetta Donati, Alessandro Pietrelli, Piero Pingitore, Paola Dongiovanni, Andrea Caddeo, Lucy Walker, Guido Baselli, Serena Pelusi, Chiara Rosso, Ester Vanni, Ann Daly, Rosellina Margherita Mancina, Antonio Grieco, Luca Miele, Stefania Grimaudo, Antonio Craxi, Salvatore Petta, Laura De Luca, Silvia Maier, Giorgio Soardo, Elisabetta Bugianesi, Fabio Colli, Renato Romagnoli, Quentin M Anstee, Helen L Reeves, Anna Ludovica Fracanzani, Silvia Fargion, Stefano Romeo, Luca Valenti
In an increasing proportion of cases, hepatocellular carcinoma (HCC) develops in patients with nonalcoholic fatty liver disease (NAFLD). Mutations in telomerase reverse transcriptase (hTERT) are associated with familial liver diseases. The aim of this study was to examine telomere length and germline hTERT mutations as associated with NAFLD-HCC. In 40 patients with NAFLD-HCC, 45 with NAFLD-cirrhosis and 64 healthy controls, peripheral blood telomere length was evaluated by qRT-PCR and hTERT coding regions and intron-exon boundaries sequenced...
August 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28659816/cardioprotective-effects-of-sirt6-in-a-mouse-model-of-transverse-aortic-constriction-induced-heart-failure
#17
Yongming Li, Xianda Meng, Wenguang Wang, Fu Liu, Zhiru Hao, Yang Yang, Jinbo Zhao, Wensi Yin, Lijuan Xu, Ruiping Zhao, Jiang Hu
SIRT6, a member of the NAD (+)-dependent class III deacetylase sirtuin family, plays important roles in the maintenance of cardiovascular homeostasis. Telomere shortening is a risk factor for age-associated diseases, including heart disease. In the present study, we investigated the role of SIRT6 and telomerase in a mouse model of transverse aortic constriction (TAC)-induced heart failure. SIRT6, telomerase reverse transcriptase (TERT), and telomere repeat binding factor (TRF)-1 were significantly downregulated in TAC mice compared with their expression in sham-operated mice...
2017: Frontiers in Physiology
https://www.readbyqxmd.com/read/28659185/the-genome-wide-transcription-response-to-telomerase-deficiency-in-the-thermotolerant-yeast-hansenula-polymorpha-dl-1
#18
Alexey V Beletsky, Alexander N Malyavko, Maria V Sukhanova, Eugenia S Mardanova, Maria I Zvereva, Olga A Petrova, Yulia Yu Parfenova, Maria P Rubtsova, Andrey V Mardanov, Olga I Lavrik, Olga A Dontsova, Nikolai V Ravin
BACKGROUND: In the course of replication of eukaryotic chromosomes, the telomere length is maintained due to activity of telomerase, the ribonucleoprotein reverse transcriptase. Abolishing telomerase function causes progressive shortening of telomeres and, ultimately, cell cycle arrest and replicative senescence. To better understand the cellular response to telomerase deficiency, we performed a transcriptomic study for the thermotolerant methylotrophic yeast Hansenula polymorpha DL-1 lacking telomerase activity...
June 28, 2017: BMC Genomics
https://www.readbyqxmd.com/read/28636941/highly-aggressive-metastatic-melanoma-cells-unable-to-maintain-telomere-length
#19
Nikenza Viceconte, Marie-Sophie Dheur, Eva Majerova, Christophe E Pierreux, Jean-François Baurain, Nicolas van Baren, Anabelle Decottignies
Unlimited replicative potential is one of the hallmarks of cancer cells. In melanoma, hTERT (telomerase reverse transcriptase) is frequently overexpressed because of activating mutations in its promoter, suggesting that telomerase is necessary for melanoma development. We observed, however, that a subset of melanoma metastases and derived cell lines had no telomere maintenance mechanism. Early passages of the latter displayed long telomeres that progressively shortened and fused before cell death. We propose that, during melanoma formation, oncogenic mutations occur in precursor melanocytes with long telomeres, providing cells with sufficient replicative potential, thereby bypassing the need to re-activate telomerase...
June 20, 2017: Cell Reports
https://www.readbyqxmd.com/read/28627628/phosphorothioate%C3%A2-modified-antisense-oligonucleotides-against-human-telomerase-reverse-transcriptase-sensitize-cancer-cells-to-radiotherapy
#20
Fei Cao, Xiaoping Ju, Di Chen, Lingong Jiang, Xiaofei Zhu, Shuiwang Qing, Fang Fang, Yuxin Shen, Zhen Jia, Huojun Zhang
Emergence of resistance, unavoidable systemic toxicity and unsatisfactory efficacy arethe main obstacles for traditional cancer therapy. Combination with phosphorothioate modified antisense oligonucleotides (PS‑ASODN) against human telomerase reverse transcriptase (hTERT) may enhance the therapeutic effect of irradiation. However, the effect of PS‑ASODN against hTERT on the anti‑tumor effects of irradiation in liver cancer remain unclear. In the current study, Walker 256 cells were transfected with hTERT PS‑ASODN...
August 2017: Molecular Medicine Reports
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