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https://www.readbyqxmd.com/read/28819549/metastatic-state-of-parent-cells-influences-the-uptake-and-functionality-of-prostate-cancer-cell-derived-extracellular-vesicles
#1
Elisa Lázaro-Ibáñez, Maarit Neuvonen, Maarit Takatalo, Uma Thanigai Arasu, Cristian Capasso, Vincenzo Cerullo, Johng S Rhim, Kirsi Rilla, Marjo Yliperttula, Pia R-M Siljander
Extracellular vesicles (EVs), including microvesicles and exosomes, mediate intercellular signalling which has a profound role in cancer progression and in the development of metastasis. Internalisation of EVs can prompt functional changes in the recipient cells, the nature of which depends on the molecular composition and the cargo of the EVs. We hypothesised that the metastatic stage of cancerous parent cells would determine the uptake efficacy and the subsequent functional effects of the respective cancer cell-derived EVs...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28819029/loss-of-the-tumor-suppressor-stag2-promotes-telomere-recombination-and-extends-the-replicative-lifespan-of-normal-human-cells
#2
Zharko Daniloski, Susan Smith
Sister chromatids are held together by cohesin, a tripartite ring with a peripheral SA1/2 subunit, where SA1 is required for telomere cohesion and SA2 for centromere cohesion. The STAG2 gene encoding SA2 is often inactivated in human cancer, but not in in a manner associated with aneuploidy. Thus, how these tumors maintain chromosomal cohesion and how STAG2 loss contributes to tumorigenesis remain open questions. Here we show that, despite a loss in centromere cohesion, sister chromatids in STAG2 mutant tumor cells maintain cohesion in mitosis at chromosome arms and telomeres...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818973/mutations-in-the-promoter-of-the-telomerase-gene-tert-contribute-to-tumorigenesis-by-a-two-step-mechanism
#3
Kunitoshi Chiba, Franziska K Lorbeer, A Hunter Shain, David T McSwiggen, Eva Schruf, Areum Oh, Jekwan Ryu, Xavier Darzacq, Boris C Bastian, Dirk Hockemeyer
TERT promoter mutations (TPMs) are the most common non-coding mutations in cancer. The timing and consequences of TPMs have not been fully established. Here we show that TPMs acquired at the transition from benign nevus to malignant melanoma do not support telomere maintenance. In vitro experiments revealed that TPMs do not prevent telomere attrition, resulting in cells with critically short and unprotected telomeres. Immortalization by TPMs requires a gradual upregulation of telomerase, coinciding with telomere fusions...
August 17, 2017: Science
https://www.readbyqxmd.com/read/28815538/long-noncoding-rnas-in-the-yeast-s-%C3%A2-cerevisiae
#4
Rachel O Niederer, Evan P Hass, David C Zappulla
Long noncoding RNAs have recently been discovered to comprise a sizeable fraction of the RNA World. The scope of their functions, physical organization, and disease relevance remain in the early stages of characterization. Although many thousands of lncRNA transcripts recently have been found to emanate from the expansive DNA between protein-coding genes in animals, there are also hundreds that have been found in simple eukaryotes. Furthermore, lncRNAs have been found in the bacterial and archaeal branches of the tree of life, suggesting they are ubiquitous...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28815372/do-trpv1-antagonists-increase-the-risk-for-skin-tumourigenesis-a-collaborative-in-vitro-and-in-vivo-assessment
#5
Miyoung Park, Anita A Naidoo, Angie Burns, Jin Kyu Choi, Kelly M Gatfield, Martin Vidgeon-Hart, Il-Hong Bae, Chang Seok Lee, Gyeyoung Choi, Andrew J Powell, Young-Ho Park, Rajni Fagg
A recent hypothesis suggesting that the pharmacological target TRPV1 (transient receptor potential vanilloid subfamily, member 1) may function as a tumour suppressor, which potentially impacts the development of TRPV1 antagonist therapeutics for a range of conditions. However, little is known about the long-term physiologic effects of TRPV1 blockade in the skin. In vitro and in vivo studies suggested that the potent TRPV1 competitive antagonist AMG-9810 promoted proliferation in N/TERT1 cells (telomerase-immortalised primary human keratinocytes 1) and tumour development in mouse skin that was mediated through EGFR/Akt/mTOR signalling...
August 16, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28815183/pinx1-is-a-potential-prognostic-factor-for-non-small-cell-lung-cancer-and-inhibits-cell-proliferation-and-migration
#6
Shengguang Wang, Hua Zhang, Jianquan Zhu, Chenguang Li, Jinfang Zhu, Bowen Shi, Bin Zhang, Changli Wang
PinX1 has been identified as a suppressor of telomerase enzymatic activity. However, the tumour-suppressive roles of PinX1 in different types of human cancers are unclear. PinX1 expression status and its correlation with clinicopathological features in non-small-cell lung cancer (NSCLC) have not been investigated. Accordingly, in this study, we aimed to evaluate the roles of PinX1 in NSCLC. PinX1 expression status was examined by immunohistochemistry using tissue microarray from a total of 158 patients. Correlations among PinX1 expression, clinicopathological variables, and patient survival were analysed...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28813500/telomere-biology-and-telomerase-mutations-in-cirrhotic-patients-with-hepatocellular-carcinoma
#7
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/28811896/effect-of-achillea-wilhelmsii-extract-on-expression-of-the-human-telomerase-reverse-transcriptase-mrna-in-the-pc3-prostate-cancer-cell-line
#8
Mojtaba Ashtiani, Fariba Nabatchian, Hamid Reza Galavi, Ramin Saravani, Farzaneh Farajian-Mashhadi, Saeedeh Salimi
Evidence has indicated that human telomerase reverse transcriptase (hTERT) was overexpressed in prostate cancer (PCa). Achillea wilhelmsii (AW) is a plant that has been traditionally used for its medicinal properties. The aim of current study was to evaluate the effects of AW extract on a PCa cell line. The cytotoxic activity of the hydroalcoholic extract of AW was studied on the PCa PC3 cell line using MTT assay. Flow cytometry was used to evaluate the effects of the extract on the apoptosis. The expression of hTERT mRNA was analyzed by the reverse transcription-quantitative polymerase chain reaction method...
September 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28810880/nlrp7-contributes-to-in-vitro-decidualization-of-endometrial-stromal-cells
#9
Jyun-Yuan Huang, Pei-Hsiu Yu, Yueh-Chun Li, Pao-Lin Kuo
BACKGROUND: Nucleotide-binding oligomerization domain (NACHT), leucine rich repeat (LRR) and pyrin domain (PYD) 7 containing protein, NLRP7, is a member of the NLR family which serves as innate immune sensors. Mutations and genetic variants of NLRP7 have been found in women with infertility associated conditions, such as recurrent hydatidiform mole, recurrent miscarriage, and preeclampsia. Decidualization of endometrial stromal cells is a hallmark of tissue remodeling to support embryo implantation and proper placental development...
August 15, 2017: Reproductive Biology and Endocrinology: RB&E
https://www.readbyqxmd.com/read/28807855/spatial-organization-and-molecular-interactions-of-the-schizosaccharomyces-pombe-ccq1-tpz1-poz1-shelterin-complex
#10
Harry Scott, Jin-Kwang Kim, Clinton Yu, Lan Huang, Feng Qiao, Derek J Taylor
The shelterin complex is a macromolecular assembly of proteins that binds to and protects telomeric DNA, which composes the ends of all linear chromosomes. Shelterin proteins prevent chromosome ends from fusing together and from eliciting erroneous induction of DNA damage response pathways. Additionally, shelterin proteins play key roles in regulating the recruitment and activation of telomerase, an enzyme that extends telomeric DNA. In fission yeast, Schizosaccharomyces pombe, interactions between the shelterin proteins Ccq1, Tpz1, and Poz1, are important for regulating telomerase-mediated telomere synthesis, and thus, telomere length homeostasis...
August 11, 2017: Journal of Molecular Biology
https://www.readbyqxmd.com/read/28799566/shrna-mediated-silencing-of-htert-suppresses-proliferation-and-promotes-apoptosis-in-osteosarcoma-cells
#11
P Chen, W-L Gu, M-Z Gong, J Wang, D-Q Li
In this study, we aim to explore the effects of short hairpin RNAs (shRNAs) targeting human telomerase reverse transcriptase (hTERT) on the proliferation and apoptosis of osteosarcoma cells. After the synthesis of shRNA that target hTERT, osteosarcoma cells were assigned into three experimental groups-shRNA group, scramble group and blank group. The transcription and expressions of the hTERT gene in transfected cells were measured with quantitative real-time polymerase chain reaction and western blotting. Cell proliferation in each group was detected by Cell Counting Kit-8 assay...
August 11, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28796247/p53-dependent-downregulation-of-htert-protein-expression-and-telomerase-activity-induces-senescence-in-lung-cancer-cells-as-a-result-of-pterostilbene-treatment
#12
Rong-Jane Chen, Pei-Hsuan Wu, Chi-Tang Ho, Tzong-Der Way, Min-Hsiung Pan, Hsiu-Min Chen, Yuan-Soon Ho, Ying-Jan Wang
Cellular senescence is characterized by permanent cell cycle arrest, triggered by a variety of stresses, such as telomerase inhibition, and it is recognized as a tumor-suppressor mechanism. In recent years, telomerase has become an important therapeutic target in several cancers; inhibition of telomerase can induce senescence via the DNA damage response (DDR). Pterostilbene (PT), a dimethyl ether analog of resveratrol, possesses a variety of biological functions, including anticancer effects; however, the molecular mechanisms underlying these effects are not fully understood...
August 10, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28795231/radiation-induced-gliomas-a-report-of-four-cases-and-analysis-of-molecular-biomarkers
#13
Tsunehito Nakao, Yasuo Sasagawa, Sumihito Nobusawa, Yasushi Takabatake, Hemragul Sabit, Masashi Kinoshita, Katsuyoshi Miyashita, Yasuhiko Hayashi, Hideaki Yokoo, Mitsutoshi Nakada
Radiation-induced glioma (RIG) is a rare secondary glioma. The tumors morphologically resemble their sporadically arising counterparts. Recently, the WHO classification of tumors of the central nervous system was revised to incorporate molecular biomarkers together with classic histological features. The status of molecular biomarkers in RIG, however, remains unclear. The objective of this study was to investigate if commonly accepted glioma-specific biomarkers are relevant in RIGs. Among 269 gliomas diagnosed as WHO grade 2, 3 and 4 in our institution, four were diagnosed as RIGs...
August 9, 2017: Brain Tumor Pathology
https://www.readbyqxmd.com/read/28792435/regulation-of-telomere-homeostasis-during-epstein-barr-virus-infection-and-immortalization
#14
REVIEW
Siamak A Kamranvar, Maria G Masucci
The acquisition of unlimited proliferative potential is dependent on the activation of mechanisms for telomere maintenance, which counteracts telomere shortening and the consequent triggering of the DNA damage response, cell cycle arrest, and apoptosis. The capacity of Epstein Barr virus (EBV) to infect B-lymphocytes in vitro and transform the infected cells into autonomously proliferating immortal cell lines underlies the association of this human gamma-herpesvirus with a broad variety of lymphoid and epithelial cell malignancies...
August 9, 2017: Viruses
https://www.readbyqxmd.com/read/28791654/pharmacotherapy-of-myelofibrosis
#15
REVIEW
Douglas Tremblay, Bridget Marcellino, John Mascarenhas
Myelofibrosis (MF) is a myeloproliferative neoplasm that is pathologically characterized by bone marrow myeloproliferation, reticulin and collagen fibrosis, and extramedullary hematopoiesis. Constitutive activation of the Janus associated kinase (JAK)-signal transducers and activators of transcription signaling pathway with resultant elevation in pro-inflammatory cytokine levels is the pathogenic hallmark of MF. JAK inhibitors, namely ruxolitinib, have been successful in alleviating symptoms and reducing splenomegaly, but therapy-related myelosuppression has led to the further development of highly selective JAK2 inhibitors...
August 8, 2017: Drugs
https://www.readbyqxmd.com/read/28782243/the-la-and-related-rna-binding-proteins-larps-structures-functions-and-evolving-perspectives
#16
REVIEW
Richard J Maraia, Sandy Mattijssen, Isabel Cruz-Gallardo, Maria R Conte
La was first identified as a polypeptide component of ribonucleic protein complexes targeted by antibodies in autoimmune patients and is now known to be a eukaryote cell-ubiquitous protein. Structure and function studies have shown that La binds to a common terminal motif, UUU-3'-OH, of nascent RNA polymerase III (RNAP III) transcripts and protects them from exonucleolytic decay. For precursor-tRNAs, the most diverse and abundant of these transcripts, La also functions as an RNA chaperone that helps to prevent their misfolding...
August 7, 2017: Wiley Interdisciplinary Reviews. RNA
https://www.readbyqxmd.com/read/28781951/ifitm1-suppresses-expression-of-human-endogenous-retroviruses-in-human-embryonic-stem-cells
#17
Yudong Fu, Zhongcheng Zhou, Hua Wang, Peng Gong, Renpeng Guo, Jinmiao Wang, Xinyi Lu, Feng Qi, Lin Liu
Interferon-induced transmembrane protein 1 (IFITM1), a member of the IFITM protein family, is a component of a multimeric complex involved in the transduction of antiproliferation and cell adhesion signals. IFITM1 is thought to play a role in antiproliferation and immune surveillance, and has been shown to restrict infection by numerous viruses. It is highly expressed in human embryonic stem cells (hESCs) but its role in hESCs remains to be elucidated. In this study, knockout of IFITM1 mediated by CRISPR/Cas9 in hESCs did not affect self-renewal, pluripotency, telomerase activity or telomeres...
August 2017: FEBS Open Bio
https://www.readbyqxmd.com/read/28780613/mec1-atr-is-needed-for-extensive-telomere-elongation-in-response-to-ethanol-in-yeast
#18
Yaniv Harari, Martin Kupiec
Telomere length homeostasis is essential for cell survival. In humans, telomeres shorten as a function of age. Short telomeres are known determinants of cell senescence and longevity. The yeast Saccharomyces cerevisiae expresses telomerase and maintains a strict telomere length homeostasis during vegetative growth. We have previously reported that different environmental signals promote changes in telomere length in S. cerevisiae. In particular, exposure to ethanol induces an extensive telomere elongation response due to a reduction in RAP1 mRNA and protein levels...
August 5, 2017: Current Genetics
https://www.readbyqxmd.com/read/28780124/antitumour-activity-of-resveratrol-on-human-melanoma-cells-a-possible-mechanism-related-to-its-interaction-with-malignant-cell-telomerase
#19
Chiara Platella, Serena Guida, Laura Bonmassar, Angelo Aquino, Enzo Bonmassar, Giampiero Ravagnan, Daniela Montesarchio, Giovanni N Roviello, Domenica Musumeci, Maria Pia Fuggetta
BACKGROUND: trans-resveratrol (tRES) is a polyphenolic stilbene found in plant products which has attracted great attention because of its antioxidant, anti-inflammatory and anticancer properties. METHODS: The possible correlation between tRES-induced suppression of melanoma cell growth and its influence on telomerase expression has been investigated by biological assays. Moreover, in order to gain new knowledge about possible mechanisms of action of tRES as antineoplastic agent, its interaction with biologically relevant secondary structure-forming DNA sequences, its aggregation properties and copper-binding activity have been studied by CD, UV and fluorescence spectroscopies...
August 2, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28776613/an-ultra-sensitive-colorimetric-assay-for-reliable-visual-detection-of-telomerase-activity
#20
Yaocai Wang, Luzhu Yang, Yanjun Wang, Wei Liu, Baoxin Li, Yan Jin
The visual detection of a disease biomarker is a promising strategy due to its simplicity and low cost, but the complexity of biological samples limits its application. Herein, a reliable and ultrasensitive colorimetric assay was proposed for detecting telomerase activity in crude cancer cell extracts. A telomerase substrate (TS) primer was immobilized onto magnetic beads (MBs) to form a MB/TS complex. In the presence of telomerase and deoxyribonucleotide triphosphates (dNTPs), the TS primer was elongated by adding multiple telomeric repeats (TTAGGG)n to the 3' end of the TS...
August 4, 2017: Analyst
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