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https://www.readbyqxmd.com/read/28300077/translational-reprogramming-in-tumour-cells-can-generate-oncoselectivity-in-viral-therapies
#1
Eneko Villanueva, Pilar Navarro, Maria Rovira-Rigau, Annarita Sibilio, Raúl Méndez, Cristina Fillat
Systemic treatment of cancer requires tumour-selective therapies that eliminate cancer cells yet preserve healthy tissues from undesired damage. Tumoral transformation is associated with profound effects in translational reprogramming of gene expression, such that tumour-specific translational regulation presents an attractive possibility for generating oncoselective therapies. We recently discovered that mRNA translational control by cytoplasmic polyadenylation element-binding proteins (CPEBs) is reactivated in cancer...
March 16, 2017: Nature Communications
https://www.readbyqxmd.com/read/28251929/transposon-insertional-mutagenesis-in-mice-identifies-human-breast-cancer-susceptibility-genes-and-signatures-for-stratification
#2
Liming Chen, Piroon Jenjaroenpun, Andrea Mun Ching Pillai, Anna V Ivshina, Ghim Siong Ow, Motakis Efthimios, Tang Zhiqun, Tuan Zea Tan, Song-Choon Lee, Keith Rogers, Jerrold M Ward, Seiichi Mori, David J Adams, Nancy A Jenkins, Neal G Copeland, Kenneth Hon-Kim Ban, Vladimir A Kuznetsov, Jean Paul Thiery
Robust prognostic gene signatures and therapeutic targets are difficult to derive from expression profiling because of the significant heterogeneity within breast cancer (BC) subtypes. Here, we performed forward genetic screening in mice using Sleeping Beauty transposon mutagenesis to identify candidate BC driver genes in an unbiased manner, using a stabilized N-terminal truncated β-catenin gene as a sensitizer. We identified 134 mouse susceptibility genes from 129 common insertion sites within 34 mammary tumors...
March 1, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28194033/integrative-analyses-of-transcriptome-sequencing-identify-novel-functional-lncrnas-in-esophageal-squamous-cell-carcinoma
#3
C-Q Li, G-W Huang, Z-Y Wu, Y-J Xu, X-C Li, Y-J Xue, Y Zhu, J-M Zhao, M Li, J Zhang, J-Y Wu, F Lei, Q-Y Wang, S Li, C-P Zheng, B Ai, Z-D Tang, C-C Feng, L-D Liao, S-H Wang, J-H Shen, Y-J Liu, X-F Bai, J-Z He, H-H Cao, B-L Wu, M-R Wang, D-C Lin, H P Koeffler, L-D Wang, X Li, E-M Li, L-Y Xu
Long non-coding RNAs (lncRNAs) have a critical role in cancer initiation and progression, and thus may mediate oncogenic or tumor suppressing effects, as well as be a new class of cancer therapeutic targets. We performed high-throughput sequencing of RNA (RNA-seq) to investigate the expression level of lncRNAs and protein-coding genes in 30 esophageal samples, comprised of 15 esophageal squamous cell carcinoma (ESCC) samples and their 15 paired non-tumor tissues. We further developed an integrative bioinformatics method, denoted URW-LPE, to identify key functional lncRNAs that regulate expression of downstream protein-coding genes in ESCC...
February 13, 2017: Oncogenesis
https://www.readbyqxmd.com/read/28179207/down-regulation-of-c-terminal-binding-protein-2-ctbp2-inhibits-proliferation-migration-and-invasion-of-human-shsy5y-cells-in-vitro
#4
Jiang Nan, Sun Guan, Xu Jin, Zhu Jian, Fu Linshan, Guo Jun
Neuroblastoma is the most common extracranial solid tumor in children and is responsible for ∼15% of pediatric cancer deaths. CtBP2 is a member of the CtBP family of proteins that functions as a transcription regulator and has been demonstrated to interact with the C-terminus of the adenoviral E1A oncoprotein. In this study, the expression of CtBP2 in the human neuroblastoma cell line SHSY5Y was down-regulated using lentiviral-mediated RNA interference. Down-regulation of CtBP2 inhibited the expression of c-myc, MMP2, and MMP9 proteins...
February 5, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28160139/erratum-to-e1a-mediated-inhibition-of-hspa5-suppresses-cell-migration-and-invasion-in-triple-negative-breast-cancer
#5
Hsin-An Chen, Yi-Wen Chang, Chi-Feng Tseng, Ching-Feng Chiu, Chih-Chen Hong, Weu Wang, Ming-Yang Wang, Michael Hsiao, Jui-Ti Ma, Chung-Hsing Chen, Shih-Sheng Jiang, Chih-Hsiung Wu, Mien-Chie Hung, Ming-Te Huang, Jen-Liang Su
No abstract text is available yet for this article.
February 3, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28122980/suppression-of-type-i-interferon-signaling-by-e1a-via-ruvbl1-pontin
#6
Oladunni Olanubi, Jasmine Rae Frost, Sandi Radko, Peter Pelka
Suppression of interferon signaling is of paramount importance to a virus. Interferon signaling will significantly reduce or halt the ability of a virus to replicate, therefore viruses have evolved sophisticated mechanisms that suppress activation of the interferon pathway or responsiveness of the infected cell to interferon. Adenovirus has multiple modes of inhibiting cellular response to interferon. Here we report that E1A, previously shown to regulate interferon signaling in multiple ways, inhibits interferon stimulated gene expression by modulating RuvBL1 function...
January 25, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28094447/on-the-origins-and-genetic-diversity-of-south-american-chickens-one-step-closer
#7
A Luzuriaga-Neira, G Villacís-Rivas, F Cueva-Castillo, G Escudero-Sánchez, A Ulloa-Nuñez, M Rubilar-Quezada, R Monteiro, M R Miller, A Beja-Pereira
Local chicken populations are a major source of food in the rural areas of South America. However, very little is known about their genetic composition and diversity. Here, we analyzed five populations from South America to investigate their maternal genetic origin and diversity, hoping to mitigate the lack of information on local chicken populations from this region. We also included three populations of chicken from the Iberian Peninsula and one from Easter Island, which are potential sources of the first chickens introduced in South America...
January 17, 2017: Animal Genetics
https://www.readbyqxmd.com/read/28075429/telomerase-specific-oncolytic-adenovirus-expressing-trail-suppresses-peritoneal-dissemination-of-gastric-cancer
#8
W Zhou, S Dai, H Zhu, Z Song, Z Han, Y Cai, J B Lee, Z Li, X Hu, B Fang, C He, X Huang
Peritoneal dissemination is the most common condition of metastasis in gastric cancer. The survival duration of a patient with advanced stage gastric cancer, may be improved by gene therapy. In this study, we used an oncolytic adenovirus vector (Ad/TRAIL-E1) that expresses both the TRAIL and E1A genes under the control of a tumor-specific promoter. We evaluated the anti-tumor effect of Ad/TRAIL-E1 on gastric cancer cells in vitro, as well as in vivo in a xenograft peritoneal carcinomatosis mouse model. Our data showed that Ad/TRAIL-E1 induced TRAIL-mediated apoptosis in gastric cancer cell lines, but not in the normal cell lines...
January 11, 2017: Gene Therapy
https://www.readbyqxmd.com/read/28074931/eid3-directly-associates-with-dnmt3a-during-transdifferentiation-of-human-umbilical-cord-mesenchymal-stem-cells-to-npc-like-cells
#9
Liang Luo, Wen-Jin Chen, James Q Yin, Ru-Xiang Xu
There has been recently been increased interest in the plasticity of human umbilical cord mesenchymal stem cells (UMSCs) and their potential in the treatment of neurological disorders. In this study, UMSCs were transdifferentiated into neural stem-like cells (uNSCL), these cells grow in neurosphere-like structures and express high levels of NSCs markers. Epigenetics-related gene screening was here used to assess the relationship between E1A-like inhibitor of differentiation 3 (EID3), a p300 inhibitor, and DNA methyltransferase 3 A (DNMT3A) during the transdifferentiation of UMSCs into uNSCL in vitro...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062494/cellular-repressor-of-e1a-stimulated-genes-is-a-critical-determinant-of-vascular-remodeling-in-response-to-angiotensin-ii
#10
Li Yang, Liu Yanxia, Tian Xiaoxiang, Zhang Yan, Song Haixu, Liu Meili, Zhang Xiaolin, Liu Haiwei, Zhang Jian, Zhang Quanyu, Liu Dan, Peng Chengfei, Yan Chenghui, Han Yaling
OBJECTIVE: Cellular repressor of E1A-stimulated genes (CREG) is a lysosomal glycoprotein implicated in maintaining vascular homeostasis. Here, we have hypothesized that CREG is a critical target of intervention for the prevention of hypertensive vascular remodeling. APPROACH AND RESULTS: CREG gene expression was significantly decreased accompanied by an upregulated expression of angiotensin II (Ang II) in remodeled vascular tissues of high salt-induced Dahl salt-sensitive rats and Ang II-induced mice...
January 5, 2017: Arteriosclerosis, Thrombosis, and Vascular Biology
https://www.readbyqxmd.com/read/28055009/expression-of-adenoviral-e1a-throws-the-pidd-switch
#11
Jay R Radke, James L Cook
No abstract text is available yet for this article.
January 5, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/27881644/suppression-of-adenovirus-replication-by-cardiotonic-steroids
#12
Filomena Grosso, Peter Stoilov, Clifford Lingwood, Martha Brown, Alan Cochrane
The dependence of adenovirus on the host pre-RNA splicing machinery for expression of its complete genome potentially makes it vulnerable to modulators of RNA splicing, such as digoxin and digitoxin. Both drugs reduced the yields of four human adenoviruses (HAdV-A31, -B35, and -C5 and a species D conjunctivitis isolate) by at least 2 to 3 logs by affecting one or more steps needed for genome replication. Immediate early E1A protein levels are unaffected by the drugs, but synthesis of the delayed protein E4orf6 and the major late capsid protein hexon is compromised...
February 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27849011/intrinsic-cellular-signaling-mechanisms-determine-the-sensitivity-of-cancer-cells-to-virus-induced-apoptosis
#13
Yunfei Wang, Dawei Li, Jian Luo, Guimei Tian, Lisa Y Zhao, Daiqing Liao
Cancer cells of epithelial and mesenchymal phenotypes exhibit different sensitivities to apoptosis stimuli, but the mechanisms underlying this phenomenon remain partly understood. We constructed a novel recombinant adenovirus expressing Ad12 E1A (Ad-E1A12) that can strongly induce apoptosis. Ad-E1A12 infection of epithelial cancer cells displayed dramatic detachment and apoptosis, whereas cancer cells of mesenchymal phenotypes with metastatic propensity were markedly more resistant to this virus. Notably, forced detachment of epithelial cells did not further sensitize them to Ad-E1A12-induced apoptosis, suggesting that cell detachment is a consequence rather than the cause of Ad-E1A12-induced apoptosis...
November 16, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27834948/the-antitumor-efficacy-of-anti-p21ras-scfv-mediated-by-the-dual-promoter-regulated-recombinant-adenovirus-kghv300
#14
X Y Pan, X J Liu, J Li, S J Zhen, D X Liu, Q Feng, W X Zhao, Y Luo, Y L Zhang, H W Li, J L Yang
Ras mutations and overexpression of the Ras protein, p21Ras, are main causes of cancer development and progression, which has made the Ras gene and p21Ras important targets for therapy of Ras-driven cancers. We previously prepared recombinant adenovirus KGHV100 based on replication-defective adenovirus type 5, which could intracellularly express anti-p21Ras single chain fragment viable antibodies (scFv) and repress tumor growth in vitro and in vivo. However, the anti-tumor effects of this anti-p21Ras scFv were limited by short-term scFv expression due to a replication defect of KGHV100...
December 22, 2016: Gene Therapy
https://www.readbyqxmd.com/read/27833761/e1a-enhances-cellular-sensitivity-to-dna-damage-induced-apoptosis-through-pidd-dependent-caspase-2-activation
#15
Jay R Radke, Zeba K Siddiqui, Iris Figueroa, James L Cook
Expression of the adenoviral protein, E1A, sensitizes mammalian cells to a wide variety of apoptosis-inducing agents through multiple cellular pathways. For example, E1A sensitizes cells to apoptosis induced by TNF-superfamily members by inhibiting NF-kappa B (NF-κB)-dependent gene expression. In contrast, E1A sensitization to nitric oxide, an inducer of the intrinsic apoptotic pathway, is not dependent upon repression of NF-κB-dependent transcription but rather is dependent upon caspase-2 activation. The latter observation suggested that E1A-induced enhancement of caspase-2 activation might be a critical factor in cellular sensitization to other intrinsic apoptosis pathway-inducing agents...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/27827000/the-role-of-alternative-gjb2-transcription-in-screening-for-neonatal-sensorineural-deafness-in-austria
#16
Thomas Parzefall, Trevor Lucas, Martin Koenighofer, Reinhard Ramsebner, Alexandra Frohne, Shelly Czeiger, Wolf-Dieter Baumgartner, Christian Schoefer, Wolfgang Gstoettner, Klemens Frei
CONCLUSION: Alterations within a novel putative Exon 1a within the gap junction beta 2 (GJB2) gene may play a role in the development of genetic hearing impairment in Austria. OBJECTIVES: Mutations in the GJB2 gene are the most common cause of hereditary sensorineural deafness. Genome-wide screening for alternative transcriptional start sites in the human genome has revealed the presence of an additional GJB2 exon (E1a). This study tested the hypothesis of whether alternative GJB2 transcription involving E1a may play a role in the development of congenital sensorineural deafness in Austria...
November 9, 2016: Acta Oto-laryngologica
https://www.readbyqxmd.com/read/27795433/efficient-transformation-of-primary-human-mesenchymal-stromal-cells-by-adenovirus-early-region-1-oncogenes
#17
Thomas Speiseder, Helga Hofmann-Sieber, Estefanía Rodríguez, Anna Schellenberg, Nuray Akyüz, Judith Dierlamm, Thilo Spruss, Claudia Lange, Thomas Dobner
Previous observations that human amniotic fluid cells (AFC) can be transformed by human adenovirus type 5 (HAdV-5) E1A/E1B oncogenes prompted us to identify the target cells in the AFC population that are susceptible to transformation. Our results demonstrate that one cell type corresponding to mesenchymal stem/stroma cells (hMSCs) can be reproducibly transformed by HAdV-5 E1A/E1B oncogenes as efficiently as primary rodent cultures. HAdV-5 E1-transformed hMSCs exhibit all properties commonly associated with a high grade of oncogenic transformation, including enhanced cell proliferation, anchorage-independent growth, increased growth rate, and high telomerase activity as well as numerical and structural chromosomal aberrations...
January 1, 2017: Journal of Virology
https://www.readbyqxmd.com/read/27784214/cellular-repressor-of-e1a-stimulated-genes-a-new-potential-therapeutic-target-for-atherosclerosis
#18
Xiaoxiang Tian, Chenghui Yan, Yaling Han
Atherosclerosis, a chronic inflammatory disease, is a major risk factor attributed to several important cardiovascular events, particularly coronary artery disease and stroke. The pathological process of atherosclerosis is considered to be dynamic and complicated, which involves into the interaction between a variety of cell types within arteries and cells that migrate into the wall. Human cellular repressor of E1A-stimulated genes (CREG) is original found as a transcription factor because it can antagonize transcriptional activation and cellular transformation induced by the adenovirus E1A oncoprotein...
October 26, 2016: Current Drug Targets
https://www.readbyqxmd.com/read/27769014/the-interaction-of-adenovirus-e1a-with-the-mammalian-protein-ku70-xrcc6
#19
Jasmine Rae Frost, Oladunni Olanubi, Stephen Ka-Hon Cheng, Andrea Soriano, Leandro Crisostomo, Alennie Lopez, Peter Pelka
Human adenovirus infects terminally differentiated cells and to replicate it must induce S-phase. The chief architects that drive adenovirus-infected cells into S-phase are the E1A proteins, with 5 different isoforms expressed during infection. E1A remodels the infected cell by associating with cellular factors and modulating their activity. The C-terminus of E1A is known to bind to only a handful of proteins. We have identified a novel E1A C-terminus binding protein, Ku70 (XRCC6), which was found to bind directly within the CR4 of E1A from human adenovirus type 5...
October 18, 2016: Virology
https://www.readbyqxmd.com/read/27699893/mapping-the-interactions-of-adenoviral-e1a-proteins-with-the-p160-nuclear-receptor-coactivator-binding-domain-of-cbp
#20
Peter Haberz, Munehito Arai, Maria A Martinez-Yamout, H Jane Dyson, Peter E Wright
Many viruses deregulate the cell and force transcription of viral genes by competing with cellular proteins for binding to the transcriptional co-activators CREB-binding protein (CBP) and p300. Through its interactions with CBP/p300 and the retinoblastoma protein, the adenovirus (AdV) early region 1A (E1A) oncoprotein hijacks the cell cycle and, in rodents, transforms the cell; the mechanistic and structural basis for these effects remain unclear. In this study we compare the affinity of protein constructs from the E1A proteins from two adenovirus serotypes, non-oncogenic AdV5 and highly oncogenic AdV12, for binding to the nuclear receptor coactivator binding domain (NCBD) of CBP...
December 2016: Protein Science: a Publication of the Protein Society
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