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https://www.readbyqxmd.com/read/29676637/epigenomic-alterations-and-gene-expression-profiles-in-human-respiratory-epithelial-cells-mediated-by-hookah-and-cigarette-smoke
#1
Yin Xiong, Sichuan Xi, Jigui Shan, Elvin Hekimoglu, Shih-Hsin Hsiao, Mary Zhang, Julie A Hong, Chris Tao, Haobin Chen, R Taylor Ripley, Chuong D Hoang, David S Schrump
RATIONALE: The effects of hookah smoke on respiratory epithelia have not been well characterized. OBJECTIVES: To characterize and compare the effects of hookah tobacco smoke and conventional cigarette smoke on the epigenome and transcriptome of human respiratory epithelia. METHODS: Normal human small airway epithelial cells and cyclin-dependent kinase 4/human telomerase reverse transcriptase-immortalized human bronchial epithelial cells were cultured for 5 days in normal media in the presence or absence of water pipe condensates or cigarette smoke condensates under relevant exposure conditions...
April 2018: Annals of the American Thoracic Society
https://www.readbyqxmd.com/read/29674449/induction-of-antitumor-cytotoxic-lymphocytes-using-engineered-human-primary-blood-dendritic-cells
#2
Long Wu, Huan Zhang, Yixing Jiang, Robert C Gallo, Hua Cheng
Dendritic cell (DC)-based cancer immunotherapy has achieved modest clinical benefits, but several technical hurdles in DC preparation, activation, and cancer/testis antigen (CTA) delivery limit its broad applications. Here, we report the development of immortalized and constitutively activated human primary blood dendritic cell lines (ihv-DCs). The ihv-DCs are a subset of CD11c+ /CD205+ DCs that constitutively display costimulatory molecules. The ihv-DCs can be genetically modified to express human telomerase reverse transcriptase (hTERT) or the testis antigen MAGEA3 in generating CTA-specific cytotoxic T lymphocytes (CTLs)...
April 19, 2018: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/29672884/oxidatively-modified-pdia3-promotes-dkc1-mediated-malignancy-and-survival-of-hepatocellular-carcinoma-cells
#3
Eunkyong Ko, Jong-Seo Kim, Soomi Ju, Hyun-Wook Seo, Yeonji Chang, Jung-Ah Kang, Sung-Gyoo Park, Guhung Jung
DKC1 is a conserved gene encoding the RNA-binding protein, dyskerin pseudouridine synthase 1, which is an essential component of the telomerase holoenzyme. DKC1 upregulation is frequently observed in many different human cancers including hepatocellular carcinoma (HCC); however, its regulatory mechanisms still remain unclear. Thus, we investigated the regulatory mechanism of DKC1 in HCC progression. We found that protein-disulfide isomerase-associated 3 (PDIA3) interacted with the DKC1 regulatory DNA in HCC cells, but not in HCC cells with elevated reactive oxygen species (ROS) levels, using liquid chromatography tandem-mass spectrometry analysis after isolating the DKC1 regulatory region binding proteins...
April 19, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29671783/telomerase-inhibition-by-a-new-synthetic-derivative-of-the-aporphine-alkaloid-boldine
#4
Sakineh Kazemi Noureini, Mitra Kheirabadi, Fatima Masoumi, Farve Khosrogerdi, Younes Zarei, Cristian Suárez-Rozas, Julio Salas-Norambuena, Bruce Kennedy Cassels
Telomerase, the enzyme responsible for cell immortality, is an important target in anti-cancer drug discovery. Boldine, an abundant aporphine alkaloid of Peumus boldus , is known to inhibit telomerase at non-toxic concentrations. Cytotoxicity of N -benzylsecoboldine hydrochloride (BSB), a synthetic derivative of boldine, was determined using the MTT method in MCF7 and MDA-MB231 cells. Aliquots of cell lysates were incubated with various concentrations of BSB in qTRAP (quantitative telomere repeat amplification protocol)-ligand experiments before substrate elongation by telomerase or amplification by hot-start Taq polymerase...
April 19, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/29669292/parn-and-toe1-constitute-a-3-end-maturation-module-for-nuclear-non-coding-rnas
#5
Ahyeon Son, Jong-Eun Park, V Narry Kim
Poly(A)-specific ribonuclease (PARN) and target of EGR1 protein 1 (TOE1) are nuclear granule-associated deadenylases, whose mutations are linked to multiple human diseases. Here, we applied mTAIL-seq and RNA sequencing (RNA-seq) to systematically identify the substrates of PARN and TOE1 and elucidate their molecular functions. We found that PARN and TOE1 do not modulate the length of mRNA poly(A) tails. Rather, they promote the maturation of nuclear small non-coding RNAs (ncRNAs). PARN and TOE1 act redundantly on some ncRNAs, most prominently small Cajal body-specific RNAs (scaRNAs)...
April 17, 2018: Cell Reports
https://www.readbyqxmd.com/read/29668478/correlation-of-htert-expression-with-cervical-cytological-abnormalities-and-human-papillomavirus-infection
#6
Vjosa A Zejnullahu, Valon A Zejnullahu, Slavica Josifovska, Nikola Vukovik, Kiril Pakovski, Sasho Panov
Telomerase Reverse Transcriptase (TERT) is the main catalytic sub-unit of telomerase, a reverse transcriptase enzyme. Telomerase expression is regulated at many levels, with numerous studies suggesting that up-regulation of human TERT gene (hTERT) at transcriptional level results in immortal cell phenotype associated with cancer. The aim of this study is to determine the correlation between hTERT expression and different cervical precursor lesions, as well as with cervical cancer in patients with confirmed Human papillomavirus (HPV) infection...
December 1, 2017: Prilozi (Makedonska Akademija Na Naukite i Umetnostite. Oddelenie za Medicinski Nauki)
https://www.readbyqxmd.com/read/29668072/a-unique-telomere-dna-expansion-phenotype-in-human-retinal-rod-photoreceptors-associated-with-aging-and-disease
#7
W Robert Bell, Alan K Meeker, Anthony Rizzo, Sumit Rajpara, Ian M Rosenthal, Miguel Flores Bellver, Silvia Aparicio Domingo, Xiufeng Zhong, John R Barber, Corinne E Joshu, M Valeria Canto-Soler, Charles G Eberhart, Christopher M Heaphy
We have identified a discrete, focal telomere DNA expansion phenotype in the photoreceptor cell layer of normal, non-neoplastic human retinas. This phenotype is similar to that observed in a subset of human cancers, including a large fraction of tumors of the central nervous system, which maintain their telomeres via the non-telomerase-mediated alternative lengthening of telomeres (ALT) mechanism. We observed that these large, ultra-bright telomere DNA foci are restricted to the rod photoreceptors and are not observed in other cell types...
April 18, 2018: Brain Pathology
https://www.readbyqxmd.com/read/29667924/telomerase-may-paradoxically-accelerate-aging-of-the-dna-methylome
#8
Andrew R Mendelsohn, James W Larrick
DNA methylation (DNAm) clocks such as the Horvath DNAm clock provide the most accurate biological determination of biological age relative to chronological age available today. However, there is little correlation between DNAm clocks, telomere-based aging clocks, and transcriptomic-based aging clocks. Recently, a genome-wide association study identified single-nucleotide polymorphism variants of TERT, the gene that encodes telomerase, as accelerating intrinsic aging in the Horvath DNAm clock. These same variants have been previously associated with long telomeres in leukocytes, suggesting that TERT acts paradoxically on telomere-associated aging and DNAm-associated aging...
April 2018: Rejuvenation Research
https://www.readbyqxmd.com/read/29667481/effects-of-ionising-radiation-on-telomere-length-and-telomerase-activity-in-cultured-human-lens-epithelium-cells
#9
Savneet Kaur Bains, Kim Chapman, Scott Bright, Anish Senan, Munira Kadhim, Predrag Slijepcevic
PURPOSE: To investigate the effects of ionising radiation on telomere length and telomerase activity in Human Lens Epithelial cells. There are studies suggesting evidence of telomere length in association with opacity of the lens, however, these studies have been conducted on Canine Lens cells. Our study was designed to understand further the effects of different doses of ionising radiation on telomere length and telomerase activity in cultured Human Lens Epithelium cells from three Donors...
April 18, 2018: International Journal of Radiation Biology
https://www.readbyqxmd.com/read/29666837/cancer-telomeres-and-white-crows
#10
REVIEW
Alan K Meeker
This mini-review article discusses past and present prostate-focused research on telomere and telomerase biology conducted at Johns Hopkins, through the eyes of a Donald S Coffey trainee. Included are past discoveries of abnormalities in telomere biology in the context of prostate cancer and its pre-malignant precursor prostatic intraepithelial neoplasia (PIN); the finding that telomerase activity is androgen-regulated in the prostate, and the potential role of telomerase in prostate epithelial stem cells. Also reviewed are more recent results showing that in situ telomere length measurements in patient tissue specimens may have utility in risk assessment and as a prognostic biomarker...
2018: American Journal of Clinical and Experimental Urology
https://www.readbyqxmd.com/read/29664790/should-we-consider-telomere-length-and-telomerase-activity-in-male-factor-infertility
#11
Carlos Balmori, Elisa Varela
PURPOSE OF REVIEW: The purpose of this review is to analyze what is known to date about the relation between telomeres and male fertility, and if it is possible for telomeres, or elements related to them, to be used as new prognostic biomarkers in fertility treatment. RECENT FINDINGS: Cells in germ series, including spermatozoids, have longer telomeres (10-20 kb), and do not seem to undergo the shortening that takes place in somatic cells with age as they present telomerase activity...
April 16, 2018: Current Opinion in Obstetrics & Gynecology
https://www.readbyqxmd.com/read/29663033/how-long-does-telomerase-extend-telomeres-regulation-of-telomerase-release-and-telomere-length-homeostasis
#12
REVIEW
Kazunori Tomita
Telomerase, the enzyme that replenishes telomeres, is essential for most eukaryotes to maintain their generations. Telomere length homeostasis is achieved via a balance between telomere lengthening by telomerase, and erosion over successive cell divisions. Impaired telomerase regulation leads to shortened telomeres and can cause defects in tissue maintenance. Telomeric DNA is composed of a repetitive sequence, which recruits the protective protein complex, shelterin. Shelterin, together with chromatin remodelling proteins, shapes the heterochromatic structure at the telomere and protects chromosome ends...
April 16, 2018: Current Genetics
https://www.readbyqxmd.com/read/29662610/human-cancer-cells-utilize-mitotic-dna-synthesis-to-resist-replication-stress-at-telomeres-regardless-of-their-telomere-maintenance-mechanism
#13
Özgün Özer, Rahul Bhowmick, Ying Liu, Ian D Hickson
Telomeres resemble common fragile sites (CFSs) in that they are difficult-to-replicate and exhibit fragility in mitosis in response to DNA replication stress. At CFSs, this fragility is associated with a delay in the completion of DNA replication until early mitosis, whereupon cells are proposed to switch to a RAD52-dependent form of break-induced replication. Here, we show that this mitotic DNA synthesis (MiDAS) is also a feature of human telomeres. Telomeric MiDAS is not restricted to those telomeres displaying overt fragility, and is a feature of a wide range of cell lines irrespective of whether their telomeres are maintained by telomerase or by the alternative lengthening of telomeres (ALT) mechanism...
March 23, 2018: Oncotarget
https://www.readbyqxmd.com/read/29657298/a-novel-long-non-coding-rna-in-the-htert-promoter-region-regulates-htert-expression
#14
Sanandan Malhotra, Mallory A Freeberg, Shelby J Winans, James Taylor, Karen L Beemon
A novel antisense transcript was identified in the human telomerase reverse transcriptase ( hTERT ) promoter region, suggesting that the hTERT promoter is bidirectional. This transcript, named hTERT antisense promoter-associated ( hTAPAS ) RNA, is a 1.6 kb long non-coding RNA. hTAPAS transcription is initiated 167 nucleotides upstream of the hTERT transcription start site and is present in both the nucleus and the cytoplasm. Surprisingly, we observed that a large fraction of the hTERT polyadenylated RNA is localized in the nucleus, suggesting this might be an additional means of regulating the cellular abundance of hTERT protein...
December 29, 2017: Non-Coding RNA
https://www.readbyqxmd.com/read/29653110/sirna-mediated-lrp-lr-knock-down-reduces-cellular-viability-of-malignant-melanoma-cells-through-the-activation-of-apoptotic-caspases
#15
Thalia M Rebelo, Leila Vania, Eloise Ferreira, Stefan F T Weiss
The 37kDa/67kDa laminin receptor (LRP/LR) is over-expressed in tumour cells and has been implicated in several tumourigenic processes such as metastasis and telomerase activation, however, more importantly the focus of the present study is on the maintenance of cellular viability and the evasion of apoptosis. The aim of the study was to investigate the role of LRP/LR on the cellular viability of early (A375) and late stage (A375SM) malignant melanoma cells. Flow cytometry and western blot analysis revealed that A375SM cells contain more cell-surface and total LRP/LR levels in comparison to the A375 cells, respectively...
April 10, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29650441/clinical-implications-of-tert-promoter-mutation-on-idh-mutation-and-mgmt-promoter-methylation-in-diffuse-gliomas
#16
Hyun Sik Kim, Mi Jung Kwon, Joon Ho Song, Eun Soo Kim, Ho Young Kim, Kyueng-Whan Min
IDH mutation and MGMT promoter methylation are reliable prognostic and predictive biomarkers in grade II-IV diffuse gliomas. Recurrent mutations in the promoter region of the telomerase reverse transcriptase (TERTp) gene have also been found in diffuse gliomas. However, the prognostic and predictive effects of TERTp mutation on IDH or MGMT status are largely unknown. IDH1/2 and TERTp mutations, as well as MGMT methylation statuses, were examined via peptide nucleic acid-mediated PCR clamping and MGMT methylation-specific PCR in 67 paraffinized tumor samples, respectively...
April 5, 2018: Pathology, Research and Practice
https://www.readbyqxmd.com/read/29649255/terra-and-the-histone-methyltransferase-dot1-cooperate-to-regulate-senescence-in-budding-yeast
#17
Jennifer J Wanat, Glennis A Logsdon, Jordan H Driskill, Zhong Deng, Paul M Lieberman, F Brad Johnson
The events underlying senescence induced by critical telomere shortening are not fully understood. Here we provide evidence that TERRA, a non-coding RNA transcribed from subtelomeres, contributes to senescence in yeast lacking telomerase (tlc1Δ). Levels of TERRA expressed from multiple telomere ends appear elevated at senescence, and expression of an artificial RNA complementary to TERRA (anti-TERRA) binds TERRA in vivo and delays senescence. Anti-TERRA acts independently from several other mechanisms known to delay senescence, including those elicited by deletions of EXO1, TEL1, SAS2, and genes encoding RNase H enzymes...
2018: PloS One
https://www.readbyqxmd.com/read/29643934/extra-telomeric-functions-of-telomerase-in-the-pathogenesis-of-epstein-barr-virus-driven-b-cell-malignancies-and-potential-therapeutic-implications
#18
REVIEW
Silvia Giunco, Maria Raffaella Petrara, Manuela Zangrossi, Andrea Celeghin, Anita De Rossi
The Epstein-Barr virus (EBV) is a ubiquitous human γ-herpesvirus causally linked to a broad spectrum of both lymphoid and epithelial malignancies. In order to maintain its persistence in host cells and promote tumorigenesis, EBV must restrict its lytic cycle, which would ultimately lead to cell death, selectively express latent viral proteins, and establish an unlimited proliferative potential. The latter step depends on the maintenance of telomere length provided by telomerase. The viral oncoprotein LMP-1 activates TERT, the catalytic component of telomerase...
2018: Infectious Agents and Cancer
https://www.readbyqxmd.com/read/29628445/the-telomerase-inhibitor-azt-enhances-differentiation-and-prevents-overgrowth-of-human-pluripotent-stem-cell-derived-neural-progenitors
#19
Yao Hu, Kai-Heng Fang, Lu-Ping Shen, Shi-Ying Cao, Fang Yuan, Yuwen Su, Min Xu, Yaoyu Chen, Yan Liu
Human pluripotent stem cell (hPSC)-based cell-replacement therapy has emerged as a promising approach for addressing numerous neurological diseases. However, hPSC transplantation has the potential to cause human cell overgrowth and cancer, which represents a major obstacle to implementing hPSC-based therapies. Inhibition of the overgrowth of transplanted cells could help reduce the risk for hPSC transplantation-induced tumorigenesis. In this study, we report that the telomerase inhibitor azidothymidine (3'-azido-3'-deoxythymidine, AZT) enhances the differentiation of cortical neurons and significantly suppresses the proliferation of hPSC-derived cortical progenitors...
April 8, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29628341/the-human-cytomegalovirus-strain-db-activates-oncogenic-pathways-in-mammary-epithelial-cells
#20
Amit Kumar, Manoj Kumar Tripathy, Sébastien Pasquereau, Fatima Al Moussawi, Wasim Abbas, Laurie Coquard, Kashif Aziz Khan, Laetitia Russo, Marie-Paule Algros, Séverine Valmary-Degano, Olivier Adotevi, Stéphanie Morot-Bizot, Georges Herbein
BACKGROUND: Human cytomegalovirus (HCMV) establishes a persistent life-long infection and increasing evidence indicates HCMV infection can modulate signaling pathways associated with oncogenesis. Breast milk is an important route of HCMV transmission in humans and we hypothesized that mammary epithelial cells could be one of the main cellular targets of HCMV infection. METHODS: The infectivity of primary human mammary epithelial cells (HMECs) was assessed following infection with the HCMV-DB strain, a clinical isolate with a marked macrophage-tropism...
March 28, 2018: EBioMedicine
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