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  1 / 159522 MEDLINE  
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[PMID]:29211796
[Au] Autor:Saison-Ridinger M; DelGiorno KE; Zhang T; Kraus A; French R; Jaquish D; Tsui C; Erikson G; Spike BT; Shokhirev MN; Liddle C; Yu RT; Downes M; Evans RM; Saghatelian A; Lowy AM; Wahl GM
[Ad] Endereço:Gene Expression Laboratory, Salk Institute for Biological Studies, La Jolla, California, United States of America.
[Ti] Título:Reprogramming pancreatic stellate cells via p53 activation: A putative target for pancreatic cancer therapy.
[So] Source:PLoS One;12(12):e0189051, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pancreatic ductal adenocarcinoma (PDAC) is characterized by an extremely dense fibrotic stroma, which contributes to tumor growth, metastasis, and drug resistance. During tumorigenesis, quiescent pancreatic stellate cells (PSCs) are activated and become major contributors to fibrosis, by increasing growth factor signaling and extracellular matrix deposition. The p53 tumor suppressor is known to restrict tumor initiation and progression through cell autonomous mechanisms including apoptosis, cell cycle arrest, and senescence. There is growing evidence that stromal p53 also exerts anti-tumor activity by paracrine mechanisms, though a role for stromal p53 in PDAC has not yet been described. Here, we demonstrate that activation of stromal p53 exerts anti-tumor effects in PDAC. We show that primary cancer-associated PSCs (caPSCs) isolated from human PDAC express wild-type p53, which can be activated by the Mdm2 antagonist Nutlin-3a. Our work reveals that p53 acts as a major regulator of PSC activation and as a modulator of PDAC fibrosis. In vitro, p53 activation by Nutlin-3a induces profound transcriptional changes, which reprogram activated PSCs to quiescence. Using immunofluorescence and lipidomics, we have also found that p53 activation induces lipid droplet accumulation in both normal and tumor-associated fibroblasts, revealing a previously undescribed role for p53 in lipid storage. In vivo, treatment of tumor-bearing mice with the clinical form of Nutlin-3a induces stromal p53 activation, reverses caPSCs activation, and decreases fibrosis. All together our work uncovers new functions for stromal p53 in PDAC.
[Mh] Termos MeSH primário: Carcinoma Ductal Pancreático/terapia
Reprogramação Celular
Genes p53
Neoplasias Pancreáticas/terapia
Células Estreladas do Pâncreas/metabolismo
[Mh] Termos MeSH secundário: Animais
Carcinoma Ductal Pancreático/metabolismo
Carcinoma Ductal Pancreático/patologia
Ésteres do Colesterol/metabolismo
Seres Humanos
Masculino
Camundongos
Camundongos Endogâmicos C57BL
Camundongos Knockout
Neoplasias Pancreáticas/metabolismo
Neoplasias Pancreáticas/patologia
Transcrição Genética
Triglicerídeos/metabolismo
Células Tumorais Cultivadas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cholesterol Esters); 0 (Triglycerides)
[Em] Mês de entrada:1712
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0189051


  2 / 159522 MEDLINE  
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[PMID]:27776265
[Au] Autor:Ianov L; Kumar A; Foster TC
[Ad] Endereço:Department of Neuroscience, McKnight Brain Institute, University of Florida, Gainesville, FL, USA; Genetics and Genomics Program, Genetics Institute, University of Florida, Gainesville, FL, USA.
[Ti] Título:Epigenetic regulation of estrogen receptor α contributes to age-related differences in transcription across the hippocampal regions CA1 and CA3.
[So] Source:Neurobiol Aging;49:79-85, 2017 Jan.
[Is] ISSN:1558-1497
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The expression of estrogen receptor alpha (ERα) varies across brain regions and changes with age and according to the previous history of estradiol exposure. ERα is regulated by a number of mechanisms including the level of mRNA (Esr1) expression. For this study, we took advantage of regional differences in hippocampal ERα expression to investigate DNA ERα promoter methylation at CpG dinucleotide sites as a potential epigenetic mechanism for regulating gene expression. Young and aged female Fischer 344 rats were ovariectomized, and Esr1 expression and ERα promoter methylation were examined in hippocampal regions CA1 and CA3, either 3 or 14 weeks following surgery. The results indicate that reduced Esr1 expression in region CA1 relative to CA3 was associated with an increase in DNA methylation in region CA1, particularly for the first CpG site. Additionally, differential methylation of distal CpG sites, 11-17, was associated with altered Esr1 expression during aging or following long-term hormone deprivation. The results support the idea that methylation of site 1 may be the primary regulatory region for cross-regional patterns in ERα expression, while distal sites are modifiable across the life span and may act as a feedback mechanism for ERα activity.
[Mh] Termos MeSH primário: Envelhecimento/genética
Envelhecimento/metabolismo
Região CA1 Hipocampal/metabolismo
Região CA3 Hipocampal/metabolismo
Epigênese Genética
Receptor alfa de Estrogênio/genética
Transcrição Genética
[Mh] Termos MeSH secundário: Animais
Metilação de DNA
Receptor alfa de Estrogênio/metabolismo
Feminino
Expressão Gênica
Regulação da Expressão Gênica no Desenvolvimento/genética
Ratos Endogâmicos F344
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Estrogen Receptor alpha)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:180311
[Lr] Data última revisão:
180311
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE


  3 / 159522 MEDLINE  
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[PMID]:29408405
[Au] Autor:Wang H; Park BS; Lim WA; Ki JS
[Ad] Endereço:Department of Biotechnology, Sangmyung University, Seoul 03016, South Korea.
[Ti] Título:CpMCA, a novel metacaspase gene from the harmful dinoflagellate Cochlodinium polykrikoides and its expression during cell death.
[So] Source:Gene;651:70-78, 2018 Apr 20.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:Metacaspases (MCAs) are cysteine proteases that share sequence homology with caspases, and may play roles in programmed cell death (PCD). In the present study, we identified a novel MCA gene (CpMCA) from the red tide dinoflagellate Cochlodinium polykrikoides, and examined its molecular characteristics and gene expression in response to algicide-induced cell death. CpMCA cDNA is 1164 bp in length, containing a dinoflagellate spliced leader sequence (dinoSL), an 879-bp open reading frame (ORF), which codes for a 293-aa protein, and a poly (A) tail. Multi-sequence comparison indicated that CpMCA belongs to type I MCA, but it has a different structure at the N-terminal. Phylogenetic analysis showed that C. polykrikoides may have acquired the MCA gene from bacteria by means of horizontal gene transfer (HGT). In addition, expressions of CpMCA significantly increased following exposure to the common algicides copper sulfate and oxidizing chlorine, which trigger cell death in dinoflagellates, suggesting that CpMCA may be involved in cell death.
[Mh] Termos MeSH primário: Caspases/genética
Dinoflagelados/genética
[Mh] Termos MeSH secundário: Morte Celular/efeitos dos fármacos
Morte Celular/genética
DNA Complementar
DNA de Protozoário
Dinoflagelados/efeitos dos fármacos
Dinoflagelados/enzimologia
Expressão Gênica
Transferência Genética Horizontal
Genes Bacterianos
Genes de Protozoários
Herbicidas/farmacologia
Filogenia
Análise de Sequência de DNA
Transcrição Genética/efeitos dos fármacos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (DNA, Complementary); 0 (DNA, Protozoan); 0 (Herbicides); EC 3.4.22.- (Caspases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180207
[St] Status:MEDLINE


  4 / 159522 MEDLINE  
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[PMID]:29208012
[Au] Autor:Pereira A; Paro R
[Ad] Endereço:Department of Biosystems Science and Engineering, ETH Zurich, 4058, Basel, Switzerland.
[Ti] Título:Pho dynamically interacts with Spt5 to facilitate transcriptional switches at the hsp70 locus.
[So] Source:Epigenetics Chromatin;10(1):57, 2017 12 06.
[Is] ISSN:1756-8935
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: Numerous target genes of the Polycomb group (PcG) are transiently activated by a stimulus and subsequently repressed. However, mechanisms by which PcG proteins regulate such target genes remain elusive. RESULTS: We employed the heat shock-responsive hsp70 locus in Drosophila to study the chromatin dynamics of PRC1 and its interplay with known regulators of the locus before, during and after heat shock. We detected mutually exclusive binding patterns for HSF and PRC1 at the hsp70 locus. We found that Pleiohomeotic (Pho), a DNA-binding PcG member, dynamically interacts with Spt5, an elongation factor. The dynamic interaction switch between Pho and Spt5 is triggered by the recruitment of HSF to chromatin. Mutation in the protein-protein interaction domain (REPO domain) of Pho interferes with the dynamics of its interaction with Spt5. The transcriptional kinetics of the heat shock response is negatively affected by a mutation in the REPO domain of Pho. CONCLUSIONS: We propose that a dynamic interaction switch between PcG proteins and an elongation factor enables stress-inducible genes to efficiently switch between ON/OFF states in the presence/absence of the activating stimulus.
[Mh] Termos MeSH primário: Proteínas Cromossômicas não Histona/metabolismo
Proteínas de Drosophila/metabolismo
Proteínas de Choque Térmico HSP70/genética
Proteínas do Grupo Polycomb/metabolismo
Fatores de Elongação da Transcrição/metabolismo
[Mh] Termos MeSH secundário: Sequência de Aminoácidos
Animais
Linhagem Celular
Cromatina/metabolismo
Proteínas de Drosophila/química
Drosophila melanogaster
Resposta ao Choque Térmico
Proteínas do Grupo Polycomb/química
Ligação Proteica
Homologia de Sequência de Aminoácidos
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Chromatin); 0 (Chromosomal Proteins, Non-Histone); 0 (Drosophila Proteins); 0 (HSP70 Heat-Shock Proteins); 0 (Polycomb-Group Proteins); 0 (Transcriptional Elongation Factors); 0 (pho protein, Drosophila); 138673-72-0 (SPT5 transcriptional elongation factor)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180310
[Lr] Data última revisão:
180310
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171207
[St] Status:MEDLINE
[do] DOI:10.1186/s13072-017-0166-9


  5 / 159522 MEDLINE  
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[PMID]:28456689
[Au] Autor:Mandic A; Strebinger D; Regali C; Phillips NE; Suter DM
[Ad] Endereço:The Institute of Bioengineering (IBI), School of Life Sciences, Swiss Federal Institute of Technology Lausanne (EPFL), 1015 Lausanne, Switzerland.
[Ti] Título:A novel method for quantitative measurements of gene expression in single living cells.
[So] Source:Methods;120:65-75, 2017 May 01.
[Is] ISSN:1095-9130
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Gene expression is at the heart of virtually any biological process, and its deregulation is at the source of numerous pathological conditions. While impressive progress has been made in genome-wide measurements of mRNA and protein expression levels, it is still challenging to obtain highly quantitative measurements in single living cells. Here we describe a novel approach based on internal tagging of endogenous proteins with a reporter allowing luminescence and fluorescence time-lapse microscopy. Using luminescence microscopy, fluctuations of protein expression levels can be monitored in single living cells with high sensitivity and temporal resolution over extended time periods. The integrated protein decay reporter allows measuring protein degradation rates in the absence of protein synthesis inhibitors, and in combination with absolute protein levels allows determining absolute amounts of proteins synthesized over the cell cycle. Finally, the internal tag can be excised by inducible expression of Cre recombinase, which enables to estimate endogenous mRNA half-lives. Our method thus opens new avenues in quantitative analysis of gene expression in single living cells.
[Mh] Termos MeSH primário: Imagem Molecular/métodos
Proteínas/genética
Análise de Célula Única/métodos
Coloração e Rotulagem/métodos
Transcrição Genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Genes Reporter/genética
Vetores Genéticos/genética
Meia-Vida
Integrases/genética
Lentivirus/genética
Luminescência
Camundongos
Microscopia de Fluorescência/métodos
Imagem Molecular/instrumentação
Proteínas/química
Proteínas/metabolismo
Proteólise
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Análise de Célula Única/instrumentação
Coloração e Rotulagem/instrumentação
Imagem com Lapso de Tempo/instrumentação
Imagem com Lapso de Tempo/métodos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Proteins); 0 (RNA, Messenger); EC 2.7.7.- (Cre recombinase); EC 2.7.7.- (Integrases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170501
[St] Status:MEDLINE


  6 / 159522 MEDLINE  
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[PMID]:28454775
[Au] Autor:Eggert F; Kulikov K; Domnick C; Leifels P; Kath-Schorr S
[Ad] Endereço:LIMES Institute, Chemical Biology & Medicinal Chemistry Unit, University of Bonn, Gerhard-Domagk-Straße 1, 53121 Bonn, Germany.
[Ti] Título:Iluminated by foreign letters - Strategies for site-specific cyclopropene modification of large functional RNAs via in vitro transcription.
[So] Source:Methods;120:17-27, 2017 May 01.
[Is] ISSN:1095-9130
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The synthesis of sequence-specifically modified long RNA molecules, which cannot entirely be prepared via solid phase synthesis methods is experimentally challenging. We are using a new approach based on an expanded genetic alphabet preparing site-specifically modified RNA molecules via standard in vitro transcription. In this report, the site-specific labeling of functional RNAs, in particular ribozymes and a long non-coding RNA with cyclopropene moieties, is presented. We provide detailed instructions for RNA labeling via in vitro transcription and include required analytical methods to verify production and identity of the transcript. We further present post-transcriptional inverse electron demand Diels-Alder cycloaddition reactions on the cyclopropene-modified sequences and discuss applications of the genetic alphabet expansion transcription for in vitro preparation of labeled functional RNAs with complex foldings. In detail, the glmS and CPEB3 ribozymes were site-specifically decorated with methyl cyclopropene moieties using the unnatural TPT3 triphosphate and were proven to be still functional. In addition, the structurally complex A region of the Xist lncRNA (401nt) was site-specifically modified with methyl cyclopropene and detected by fluorescence after cycloaddition reaction with a tetrazine-BODIPY conjugate.
[Mh] Termos MeSH primário: Reação de Cicloadição/métodos
Ciclopropanos/química
RNA Catalítico/química
RNA Longo não Codificante/química
Coloração e Rotulagem/métodos
[Mh] Termos MeSH secundário: Elétrons
Corantes Fluorescentes/química
Técnicas In Vitro/métodos
Nucleotídeos/química
Processamento Pós-Transcricional do RNA
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cyclopropanes); 0 (Fluorescent Dyes); 0 (Nucleotides); 0 (RNA, Catalytic); 0 (RNA, Long Noncoding); J6UJO23JGU (1-methylcyclopropene)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180309
[Lr] Data última revisão:
180309
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  7 / 159522 MEDLINE  
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[PMID]:29434199
[Au] Autor:Hayashi T; Ozaki H; Sasagawa Y; Umeda M; Danno H; Nikaido I
[Ad] Endereço:Bioinformatics Research Unit, Advanced Center for Computing and Communication, RIKEN, 2-1 Hirosawa Wako, Saitama, 351-0198, Japan.
[Ti] Título:Single-cell full-length total RNA sequencing uncovers dynamics of recursive splicing and enhancer RNAs.
[So] Source:Nat Commun;9(1):619, 2018 02 12.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Total RNA sequencing has been used to reveal poly(A) and non-poly(A) RNA expression, RNA processing and enhancer activity. To date, no method for full-length total RNA sequencing of single cells has been developed despite the potential of this technology for single-cell biology. Here we describe random displacement amplification sequencing (RamDA-seq), the first full-length total RNA-sequencing method for single cells. Compared with other methods, RamDA-seq shows high sensitivity to non-poly(A) RNA and near-complete full-length transcript coverage. Using RamDA-seq with differentiation time course samples of mouse embryonic stem cells, we reveal hundreds of dynamically regulated non-poly(A) transcripts, including histone transcripts and long noncoding RNA Neat1. Moreover, RamDA-seq profiles recursive splicing in >300-kb introns. RamDA-seq also detects enhancer RNAs and their cell type-specific activity in single cells. Taken together, we demonstrate that RamDA-seq could help investigate the dynamics of gene expression, RNA-processing events and transcriptional regulation in single cells.
[Mh] Termos MeSH primário: Sequenciamento de Nucleotídeos em Larga Escala/métodos
Células-Tronco Embrionárias Murinas/metabolismo
Processamento de RNA
RNA Longo não Codificante/genética
RNA Mensageiro/genética
Análise de Célula Única/métodos
[Mh] Termos MeSH secundário: Animais
Sequência de Bases
Diferenciação Celular
Elementos Facilitadores Genéticos
Éxons
Histonas/genética
Histonas/metabolismo
Íntrons
Camundongos
Células-Tronco Embrionárias Murinas/citologia
RNA Longo não Codificante/metabolismo
RNA Mensageiro/metabolismo
Análise de Sequência de RNA
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Histones); 0 (NEAT1 long non-coding RNA, mouse); 0 (RNA, Long Noncoding); 0 (RNA, Messenger)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180307
[Lr] Data última revisão:
180307
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180214
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-018-02866-0


  8 / 159522 MEDLINE  
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[PMID]:29348663
[Au] Autor:Miao Y; Ajami NE; Huang TS; Lin FM; Lou CH; Wang YT; Li S; Kang J; Munkacsi H; Maurya MR; Gupta S; Chien S; Subramaniam S; Chen Z
[Ad] Endereço:Department of Diabetes Complications and Metabolism, Beckman Research Institute, City of Hope, 1500 Duarte Rd., Duarte, CA, 91010, USA.
[Ti] Título:Enhancer-associated long non-coding RNA LEENE regulates endothelial nitric oxide synthase and endothelial function.
[So] Source:Nat Commun;9(1):292, 2018 01 18.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:The optimal expression of endothelial nitric oxide synthase (eNOS), the hallmark of endothelial homeostasis, is vital to vascular function. Dynamically regulated by various stimuli, eNOS expression is modulated at transcriptional, post-transcriptional, and post-translational levels. However, epigenetic modulations of eNOS, particularly through long non-coding RNAs (lncRNAs) and chromatin remodeling, remain to be explored. Here we identify an enhancer-associated lncRNA that enhances eNOS expression (LEENE). Combining RNA-sequencing and chromatin conformation capture methods, we demonstrate that LEENE is co-regulated with eNOS and that its enhancer resides in proximity to eNOS promoter in endothelial cells (ECs). Gain- and Loss-of-function of LEENE differentially regulate eNOS expression and EC function. Mechanistically, LEENE facilitates the recruitment of RNA Pol II to the eNOS promoter to enhance eNOS nascent RNA transcription. Our findings unravel a new layer in eNOS regulation and provide novel insights into cardiovascular regulation involving endothelial function.
[Mh] Termos MeSH primário: Células Endoteliais/metabolismo
Elementos Facilitadores Genéticos/genética
Regulação Enzimológica da Expressão Gênica
Óxido Nítrico Sintase Tipo III/genética
RNA Longo não Codificante/genética
[Mh] Termos MeSH secundário: Animais
Células Cultivadas
Perfilação da Expressão Gênica
Seres Humanos
Masculino
Camundongos Endogâmicos C57BL
Óxido Nítrico Sintase Tipo III/metabolismo
Regiões Promotoras Genéticas/genética
RNA Polimerase II/metabolismo
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (RNA, Long Noncoding); 0 (long non-coding RNA LEENE, human); EC 1.14.13.39 (Nitric Oxide Synthase Type III); EC 2.7.7.- (RNA Polymerase II)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180120
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02113-y


  9 / 159522 MEDLINE  
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[PMID]:28455144
[Au] Autor:Zhang F; Lu YX; Chen Q; Zou HM; Zhang JM; Hu YH; Li XM; Zhang WJ; Zhang W; Lin C; Li XN
[Ad] Endereço:Department of Pathology, School of Basic Medical Sciences, Southern Medical University, Guangzhou 510515, China. Electronic address: zfan1985@yeah.net.
[Ti] Título:Identification of NCK1 as a novel downstream effector of STAT3 in colorectal cancer metastasis and angiogenesis.
[So] Source:Cell Signal;36:67-78, 2017 Aug.
[Is] ISSN:1873-3913
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Signal transducer and activator of transcription 3 (STAT3) is known to activate targets associated with invasion, proliferation, and angiogenesis in a wide variety of cancers. The adaptor protein NCK1 is involved in cytoskeletal movement and was identified as a STAT3-associated target in human tumors. However, the underlying molecular mechanism associated with colorectal cancer (CRC) metastasis is not yet completely understood. In this study, we report a novel STAT3 to NCK1 signaling pathway in colorectal cancer (CRC). We investigated the expression of NCK1 and its potential clinical and biological significance in CRC. NCK1 was noticeably up-regulated in human CRC tissues. NCK1 was also significantly associated with serosal invasion, lymph metastasis, and tumor-node-metastasis classification but was inversely correlated with differentiation. Gain-of-function and loss-of-function studies have shown that ectopic expression of NCK1 enhanced metastasis and angiogenesis in CRC cells. By gene expression analyses, we revealed a high co-overexpression of STAT3 and NCK1 in CRC tissues. Ectopic overexpression of STAT3 in CRC cells induced the expression of NCK1, whereas STAT3 knockdown decreased the expression of NCK1. Promoter activation and binding analyses demonstrated that STAT3 promoted the expression of NCK1 via direct action on the NCK1 promoter. The knock down of NCK1 partially reduced the CRC cell metastasis and angiogenesis promoted by STAT3. Additionally, by co-immunoprecipitation assays, we verified that NCK1 interacted with PAK1, which resulted in the activation of the PAK1/ERK pathway. STAT3 induced the transcription of NCK1 and triggered a PAK1/ERK cascade in CRC. These findings suggest a novel STAT3 to NCK1 to PAK1/ERK signaling mechanism that is potentially critical for CRC metastasis and angiogenesis.
[Mh] Termos MeSH primário: Proteínas Adaptadoras de Transdução de Sinal/metabolismo
Neoplasias Colorretais/irrigação sanguínea
Neoplasias Colorretais/patologia
Metástase Linfática/patologia
Neovascularização Patológica/metabolismo
Proteínas Oncogênicas/metabolismo
Fator de Transcrição STAT3/metabolismo
[Mh] Termos MeSH secundário: Proteínas Adaptadoras de Transdução de Sinal/genética
Animais
Movimento Celular
Galinhas
Neoplasias Colorretais/genética
MAP Quinases Reguladas por Sinal Extracelular/metabolismo
Feminino
Quinase 2 de Adesão Focal/metabolismo
Regulação Neoplásica da Expressão Gênica
Técnicas de Silenciamento de Genes
Células Endoteliais da Veia Umbilical Humana
Seres Humanos
Masculino
Camundongos Nus
Meia-Idade
Proteínas Oncogênicas/genética
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Adaptor Proteins, Signal Transducing); 0 (Nck protein); 0 (Oncogene Proteins); 0 (STAT3 Transcription Factor); EC 2.7.10.2 (Focal Adhesion Kinase 2); EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180306
[Lr] Data última revisão:
180306
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170430
[St] Status:MEDLINE


  10 / 159522 MEDLINE  
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[PMID]:29302024
[Au] Autor:Chen Y; Ho JML; Shis DL; Gupta C; Long J; Wagner DS; Ott W; Josic K; Bennett MR
[Ad] Endereço:Department of Biosciences, Rice University, 6100 Main Street, Houston, TX, 77005, USA.
[Ti] Título:Tuning the dynamic range of bacterial promoters regulated by ligand-inducible transcription factors.
[So] Source:Nat Commun;9(1):64, 2018 01 04.
[Is] ISSN:2041-1723
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:One challenge for synthetic biologists is the predictable tuning of genetic circuit regulatory components to elicit desired outputs. Gene expression driven by ligand-inducible transcription factor systems must exhibit the correct ON and OFF characteristics: appropriate activation and leakiness in the presence and absence of inducer, respectively. However, the dynamic range of a promoter (i.e., absolute difference between ON and OFF states) is difficult to control. We report a method that tunes the dynamic range of ligand-inducible promoters to achieve desired ON and OFF characteristics. We build combinatorial sets of AraC-and LasR-regulated promoters containing -10 and -35 sites from synthetic and Escherichia coli promoters. Four sequence combinations with diverse dynamic ranges were chosen to build multi-input transcriptional logic gates regulated by two and three ligand-inducible transcription factors (LacI, TetR, AraC, XylS, RhlR, LasR, and LuxR). This work enables predictable control over the dynamic range of regulatory components.
[Mh] Termos MeSH primário: Proteínas de Escherichia coli/genética
Escherichia coli/genética
Regulação Bacteriana da Expressão Gênica
Regiões Promotoras Genéticas/genética
Fatores de Transcrição/genética
[Mh] Termos MeSH secundário: Algoritmos
Escherichia coli/metabolismo
Proteínas de Escherichia coli/metabolismo
Ligantes
Modelos Genéticos
Termodinâmica
Fatores de Transcrição/metabolismo
Transcrição Genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, N.I.H., EXTRAMURAL; RESEARCH SUPPORT, NON-U.S. GOV'T; RESEARCH SUPPORT, U.S. GOV'T, NON-P.H.S.
[Nm] Nome de substância:
0 (Escherichia coli Proteins); 0 (Ligands); 0 (Transcription Factors)
[Em] Mês de entrada:1803
[Cu] Atualização por classe:180305
[Lr] Data última revisão:
180305
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:180106
[St] Status:MEDLINE
[do] DOI:10.1038/s41467-017-02473-5



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