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Pesquisa : D08.811.913.696.630.700 [Categoria DeCS]
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  1 / 2216 MEDLINE  
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[PMID]:27774669
[Au] Autor:Hu H; Zhu W; Qin J; Chen M; Gong L; Li L; Liu X; Tao Y; Yin H; Zhou H; Zhou L; Ye D; Ye Q; Gao D
[Ad] Endereço:CAS Key Laboratory of Systems Biology, Innovation Center for Cell Signaling Network, CAS Center for Excellence in Molecular Cell Science, Institute of Biochemistry and Cell Biology, Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, Shanghai, China.
[Ti] Título:Acetylation of PGK1 promotes liver cancer cell proliferation and tumorigenesis.
[So] Source:Hepatology;65(2):515-528, 2017 Feb.
[Is] ISSN:1527-3350
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Phosphoglycerate kinase 1 (PGK1) is an important enzyme in the metabolic glycolysis pathway. In this study, we observed a significant overexpression of PGK1 in liver cancer tissues and a negative correlation between PGK1 expression and liver cancer patient survival. Furthermore, depletion of PGK1 dramatically reduced cancer cell proliferation and tumorigenesis, indicating an oncogenic role of PGK1 in liver cancer progression. Moreover, we identified acetylation at the K323 site of PGK1 as an important regulatory mechanism for promoting its enzymatic activity and cancer cell metabolism. And we further characterized P300/cyclic adenosine monophosphate response element binding protein-binding protein-associated factor (PCAF) and Sirtuin 7 as the enzymes regulating K323 acetylation from both directions in liver cancer cells. CONCLUSION: These findings demonstrate a novel regulation of PGK1 as well as its important role in liver cancer progression. (Hepatology 2017;65:515-528).
[Mh] Termos MeSH primário: Acetilação/efeitos dos fármacos
Carcinogênese/genética
Carcinoma Hepatocelular/patologia
Neoplasias Hepáticas/patologia
Fosfoglicerato Quinase/genética
[Mh] Termos MeSH secundário: Carcinoma Hepatocelular/fisiopatologia
Linhagem Celular Tumoral/metabolismo
Linhagem Celular Tumoral/patologia
Regulação Neoplásica da Expressão Gênica
Glicólise/genética
Seres Humanos
Estimativa de Kaplan-Meier
Neoplasias Hepáticas/fisiopatologia
Modelos de Riscos Proporcionais
Técnicas de Cultura de Tecidos
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.2.3 (Phosphoglycerate Kinase)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:180122
[Lr] Data última revisão:
180122
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161025
[St] Status:MEDLINE
[do] DOI:10.1002/hep.28887


  2 / 2216 MEDLINE  
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[PMID]:28457968
[Au] Autor:Xu D; Aka JA; Wang R; Lin SX
[Ad] Endereço:Laboratory of Molecular Endocrinology and Oncology, Centre Hospitalier Universitaire de Québec Research Centre (CHUQ, CHUL) and Department of Molecular Medicine, Laval University, 2705 Boulevard Laurier, Quebec City, Québec G1V 4G2, Canada.
[Ti] Título:17beta-hydroxysteroid dehydrogenase type 5 is negatively correlated to apoptosis inhibitor GRP78 and tumor-secreted protein PGK1, and modulates breast cancer cell viability and proliferation.
[So] Source:J Steroid Biochem Mol Biol;171:270-280, 2017 07.
[Is] ISSN:1879-1220
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:17beta-hydroxysteroid dehydrogenase type 5 (17ß-HSD5) is an important enzyme associated with sex steroid metabolism in hormone-dependent cancer. However, reports on its expression and its prognostic value in breast cancer are inconsistent. Here, we demonstrate the impact of 17ß-HSD5 expression modulation on the proteome of estrogen receptor-positive (ER+) breast cancer cells. RNA interference technique (siRNA) was used to knock down 17ß-HSD5 gene expression in the ER+ breast cancer cell line MCF-7 and the proteome of the 17ß-HSD5-knockdown cells was compared to that of MCF-7 cells using two-dimensional (2-D) gel electrophoresis followed by mass spectrometry analysis. Ingenuity pathway analysis (IPA) was additionally used to assess functional enrichment analyses of the proteomic dataset, including protein network and canonical pathways. Our proteomic analysis revealed only four differentially expressed protein spots (fold change > 2, p<0.05) between the two cell lines. The four spots were up-regulated in 17ß-HSD5-knockdown MCF-7 cells, and comprised 21 proteins involved in two networks and in functions that include apoptosis inhibition, regulation of cell growth and differentiation, signal transduction and tumor metastasis. Among the proteins are nucleoside diphosphate kinase A (NME1), 78kDa glucose-regulated protein (GRP78) and phosphoglycerate kinase 1 (PGK1). We also showed that expression of 17ß-HSD5 and that of the apoptosis inhibitor GRP78 are strongly but negatively correlated. Consistent with their opposite regulation, GRP78 knockdown decreased MCF-7 cell viability whereas 17ß-HSD5 knockdown or inhibition increased cell viability and proliferation. Besides, IPA analysis revealed that ubiquitination pathway is significantly affected by 17ß-HSD5 knockdown. Furthermore, IPA predicted the proto-oncogene c-Myc as an upstream regulator linked to the tumor-secreted protein PGK1. The latter is over-expressed in invasive ductal breast carcinoma as compared with normal breast tissue and its expression increased following 17ß-HSD5 knockdown. Our present results indicate a 17ß-HSD5 role in down-regulating breast cancer development. We thus propose that 17ß-HSD5 may not be a potent target for breast cancer treatment but its low expression could represent a poor prognosis factor.
[Mh] Termos MeSH primário: 3-Hidroxiesteroide Desidrogenases/metabolismo
Neoplasias da Mama/metabolismo
Regulação Neoplásica da Expressão Gênica
Proteínas de Choque Térmico/metabolismo
Hidroxiprostaglandina Desidrogenases/metabolismo
Proteínas de Neoplasias/metabolismo
Fosfoglicerato Quinase/metabolismo
[Mh] Termos MeSH secundário: 3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores
3-Hidroxiesteroide Desidrogenases/química
3-Hidroxiesteroide Desidrogenases/genética
Membro C3 da Família 1 de alfa-Ceto Redutase
Neoplasias da Mama/patologia
Proliferação Celular
Sobrevivência Celular
Ativação Enzimática
Feminino
Perfilação da Expressão Gênica
Proteínas de Choque Térmico/antagonistas & inibidores
Proteínas de Choque Térmico/química
Proteínas de Choque Térmico/genética
Seres Humanos
Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores
Hidroxiprostaglandina Desidrogenases/química
Hidroxiprostaglandina Desidrogenases/genética
Processamento de Imagem Assistida por Computador
Células MCF-7
Nucleosídeo NM23 Difosfato Quinases/química
Nucleosídeo NM23 Difosfato Quinases/genética
Nucleosídeo NM23 Difosfato Quinases/metabolismo
Proteínas de Neoplasias/antagonistas & inibidores
Proteínas de Neoplasias/química
Proteínas de Neoplasias/genética
Fosfoglicerato Quinase/química
Fosfoglicerato Quinase/genética
Proteômica/métodos
Proteínas Proto-Oncogênicas c-myc/química
Proteínas Proto-Oncogênicas c-myc/genética
Proteínas Proto-Oncogênicas c-myc/metabolismo
Interferência de RNA
Receptores Estrogênicos/metabolismo
Eletroforese em Gel Diferencial Bidimensional
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (Heat-Shock Proteins); 0 (MYC protein, human); 0 (NM23 Nucleoside Diphosphate Kinases); 0 (Neoplasm Proteins); 0 (Proto-Oncogene Proteins c-myc); 0 (Receptors, Estrogen); 0 (molecular chaperone GRP78); EC 1.1.- (3-Hydroxysteroid Dehydrogenases); EC 1.1.1.- (Hydroxyprostaglandin Dehydrogenases); EC 1.1.1.357 (AKR1C3 protein, human); EC 1.1.1.357 (Aldo-Keto Reductase Family 1 Member C3); EC 2.7.2.3 (PGK1 protein, human); EC 2.7.2.3 (Phosphoglycerate Kinase); EC 2.7.4.6 (NME1 protein, human)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171208
[Lr] Data última revisão:
171208
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170502
[St] Status:MEDLINE


  3 / 2216 MEDLINE  
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[PMID]:29059239
[Au] Autor:Prasanth KR; Chuang C; Nagy PD
[Ad] Endereço:Department of Plant Pathology, University of Kentucky, Plant Science Building, Lexington, KY, United States of America.
[Ti] Título:Co-opting ATP-generating glycolytic enzyme PGK1 phosphoglycerate kinase facilitates the assembly of viral replicase complexes.
[So] Source:PLoS Pathog;13(10):e1006689, 2017 Oct.
[Is] ISSN:1553-7374
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The intricate interactions between viruses and hosts include exploitation of host cells for viral replication by using many cellular resources, metabolites and energy. Tomato bushy stunt virus (TBSV), similar to other (+)RNA viruses, induces major changes in infected cells that lead to the formation of large replication compartments consisting of aggregated peroxisomal and ER membranes. Yet, it is not known how TBSV obtains the energy to fuel these energy-consuming processes. In the current work, the authors discovered that TBSV co-opts the glycolytic ATP-generating Pgk1 phosphoglycerate kinase to facilitate the assembly of new viral replicase complexes. The recruitment of Pgk1 into the viral replication compartment is through direct interaction with the viral replication proteins. Altogether, we provide evidence that the ATP generated locally within the replication compartment by the co-opted Pgk1 is used to fuel the ATP-requirement of the co-opted heat shock protein 70 (Hsp70) chaperone, which is essential for the assembly of new viral replicase complexes and the activation of functional viral RNA-dependent RNA polymerase. The advantage of direct recruitment of Pgk1 into the virus replication compartment could be that the virus replicase assembly does not need to intensively compete with cellular processes for access to ATP. In addition, local production of ATP within the replication compartment could greatly facilitate the efficiency of Hsp70-driven replicase assembly by providing high ATP concentration within the replication compartment.
[Mh] Termos MeSH primário: Interações Hospedeiro-Patógeno/fisiologia
Fosfoglicerato Quinase/metabolismo
Tombusvirus/crescimento & desenvolvimento
Montagem de Vírus/fisiologia
[Mh] Termos MeSH secundário: RNA Replicase/metabolismo
Saccharomyces cerevisiae
Tabaco/virologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 2.7.2.3 (Phosphoglycerate Kinase); EC 2.7.7.48 (RNA Replicase)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171113
[Lr] Data última revisão:
171113
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171024
[St] Status:MEDLINE
[do] DOI:10.1371/journal.ppat.1006689


  4 / 2216 MEDLINE  
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[PMID]:29045475
[Au] Autor:Dou X; Gao J; Gao P; Tang D; Peng D; Mao J; Huang Z; Chen P; Chen H; Ke S; Liang C; Zhang X
[Ad] Endereço:Department of Urology, the First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China.
[Ti] Título:Association between RNA-binding protein Ptbp2 and germ cell injury in an experimentally-induced unilateral cryptorchidism murine model.
[So] Source:PLoS One;12(10):e0186654, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:RNA binding protein polypyrimidine tract binding protein 2 (Ptbp2) as a key alternative splicing regulator for male germ cell development is well established. However, its expression levels and role in cryptorchidism testes tissues has not been explored. Additionally, the molecular mechanism of heat stress impacts the correct proliferation and differentiation of germ cells is unclear. To investigate whether changes in Ptbp2 expression are correlated with heat stress-induced germ cell injury in testicular tissue, we used a murine model of intraperitoneal cryptorchidism with surgical operation. Here we present compelling evidence that germ cells are severely damaged in mice with unilateral cryptorchidism, with non-obstructive azoospermia. And the Ptbp2 and Pgk2 mRNA levels were significantly decreased in parallel, leading us to conclude that the negative correlation between Ptbp2 levels and germ cell injury in unilateral cryptorchidism murine model. We hypothesize that Ptbp2 is susceptible to heat stress and its disruption has resulted in stability decline of germ cell transcripts Pgk2 mRNA, which consequently lead to germ cell injury in cryptorchidism testes. Thus, we confirm that Ptbp2 is an essential factor in heat stress-induced sperm cell injury and non-obstructive azoospermia.
[Mh] Termos MeSH primário: Criptorquidismo/metabolismo
Criptorquidismo/patologia
Isoenzimas/metabolismo
Fosfoglicerato Quinase/metabolismo
Espermatozoides/metabolismo
Espermatozoides/patologia
[Mh] Termos MeSH secundário: Animais
Contagem de Células
Criptorquidismo/genética
Modelos Animais de Doenças
Epididimo/metabolismo
Epididimo/patologia
Imuno-Histoquímica
Isoenzimas/genética
Masculino
Camundongos Endogâmicos ICR
Proteínas do Tecido Nervoso/metabolismo
Tamanho do Órgão
Fosfoglicerato Quinase/genética
Proteína de Ligação a Regiões Ricas em Polipirimidinas/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Reação em Cadeia da Polimerase em Tempo Real
Testículo/metabolismo
Testículo/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Isoenzymes); 0 (Nerve Tissue Proteins); 0 (Ptbp2 protein, mouse); 0 (RNA, Messenger); 139076-35-0 (Polypyrimidine Tract-Binding Protein); EC 2.7.2.3 (Phosphoglycerate Kinase); EC 2.7.2.3 (phosphoglycerate kinase, testis specific)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171031
[Lr] Data última revisão:
171031
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171019
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0186654


  5 / 2216 MEDLINE  
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[PMID]:28635653
[Au] Autor:Xia J; Feng B; Shao Q; Yuan Y; Wang XS; Chen N; Wu S
[Ad] Endereço:State Key Laboratory of Bioactive Substance and Function of Natural Medicines, Department of New Drug Research and Development, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. jiexia@imm.ac.cn.
[Ti] Título:Virtual Screening against Phosphoglycerate Kinase 1 in Quest of Novel Apoptosis Inhibitors.
[So] Source:Molecules;22(6), 2017 Jun 21.
[Is] ISSN:1420-3049
[Cp] País de publicação:Switzerland
[La] Idioma:eng
[Ab] Resumo:Inhibition of apoptosis is a potential therapy to treat human diseases such as neurodegenerative disorders (e.g., Parkinson's disease), stroke, and sepsis. Due to the lack of druggable targets, it remains a major challenge to discover apoptosis inhibitors. The recent repositioning of a marketed drug (i.e., terazosin) as an anti-apoptotic agent uncovered a novel target (i.e., human phosphoglycerate kinase 1 (hPgk1)). In this study, we developed a virtual screening (VS) pipeline based on the X-ray structure of Pgk1/terazosin complex and applied it to a screening campaign for potential anti-apoptotic agents. The hierarchical filters in the pipeline (i.e., similarity search, a pharmacophore model, a shape-based model, and molecular docking) rendered 13 potential hits from Specs chemical library. By using PC12 cells (exposed to rotenone) as a cell model for bioassay, we first identified that AK-918/42829299, AN-465/41520984, and AT-051/43421517 were able to protect PC12 cells from rotenone-induced cell death. Molecular docking suggested these hit compounds were likely to bind to hPgk1 in a similar mode to terazosin. In summary, we not only present a versatile VS pipeline for potential apoptosis inhibitors discovery, but also provide three novel-scaffold hit compounds that are worthy of further development and biological study.
[Mh] Termos MeSH primário: Apoptose/efeitos dos fármacos
Avaliação Pré-Clínica de Medicamentos/métodos
Fosfoglicerato Quinase/antagonistas & inibidores
Fosfoglicerato Quinase/metabolismo
Prazosina/análogos & derivados
Inibidores de Proteínas Quinases/farmacologia
[Mh] Termos MeSH secundário: Animais
Sobrevivência Celular/efeitos dos fármacos
Bases de Dados de Compostos Químicos
Seres Humanos
Modelos Moleculares
Simulação de Acoplamento Molecular/métodos
Células PC12
Fosfoglicerato Quinase/química
Prazosina/química
Prazosina/metabolismo
Prazosina/farmacologia
Inibidores de Proteínas Quinases/química
Inibidores de Proteínas Quinases/metabolismo
Ratos
Bibliotecas de Moléculas Pequenas
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Kinase Inhibitors); 0 (Small Molecule Libraries); 8L5014XET7 (Terazosin); EC 2.7.2.3 (PGK1 protein, human); EC 2.7.2.3 (Phosphoglycerate Kinase); XM03YJ541D (Prazosin)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171117
[Lr] Data última revisão:
171117
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170622
[St] Status:MEDLINE


  6 / 2216 MEDLINE  
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[PMID]:28426667
[Au] Autor:Boyd PJ; Tu WY; Shorrock HK; Groen EJN; Carter RN; Powis RA; Thomson SR; Thomson D; Graham LC; Motyl AAL; Wishart TM; Highley JR; Morton NM; Becker T; Becker CG; Heath PR; Gillingwater TH
[Ad] Endereço:Euan MacDonald Centre for Motor Neurone Disease Research, University of Edinburgh, Edinburgh, United Kingdom.
[Ti] Título:Bioenergetic status modulates motor neuron vulnerability and pathogenesis in a zebrafish model of spinal muscular atrophy.
[So] Source:PLoS Genet;13(4):e1006744, 2017 Apr.
[Is] ISSN:1553-7404
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Degeneration and loss of lower motor neurons is the major pathological hallmark of spinal muscular atrophy (SMA), resulting from low levels of ubiquitously-expressed survival motor neuron (SMN) protein. One remarkable, yet unresolved, feature of SMA is that not all motor neurons are equally affected, with some populations displaying a robust resistance to the disease. Here, we demonstrate that selective vulnerability of distinct motor neuron pools arises from fundamental modifications to their basal molecular profiles. Comparative gene expression profiling of motor neurons innervating the extensor digitorum longus (disease-resistant), gastrocnemius (intermediate vulnerability), and tibialis anterior (vulnerable) muscles in mice revealed that disease susceptibility correlates strongly with a modified bioenergetic profile. Targeting of identified bioenergetic pathways by enhancing mitochondrial biogenesis rescued motor axon defects in SMA zebrafish. Moreover, targeting of a single bioenergetic protein, phosphoglycerate kinase 1 (Pgk1), was found to modulate motor neuron vulnerability in vivo. Knockdown of pgk1 alone was sufficient to partially mimic the SMA phenotype in wild-type zebrafish. Conversely, Pgk1 overexpression, or treatment with terazosin (an FDA-approved small molecule that binds and activates Pgk1), rescued motor axon phenotypes in SMA zebrafish. We conclude that global bioenergetics pathways can be therapeutically manipulated to ameliorate SMA motor neuron phenotypes in vivo.
[Mh] Termos MeSH primário: Neurônios Motores/metabolismo
Atrofia Muscular Espinal/metabolismo
Fosfoglicerato Quinase/genética
Medula Espinal/metabolismo
Proteína 1 de Sobrevivência do Neurônio Motor/genética
[Mh] Termos MeSH secundário: Trifosfato de Adenosina/metabolismo
Animais
Axônios/metabolismo
Axônios/patologia
Modelos Animais de Doenças
Suscetibilidade a Doenças
Metabolismo Energético
Regulação da Expressão Gênica no Desenvolvimento
Seres Humanos
Camundongos
Mitocôndrias/metabolismo
Neurônios Motores/efeitos dos fármacos
Músculo Esquelético/metabolismo
Músculo Esquelético/patologia
Atrofia Muscular Espinal/genética
Atrofia Muscular Espinal/fisiopatologia
Fosfoglicerato Quinase/antagonistas & inibidores
Prazosina/administração & dosagem
Prazosina/análogos & derivados
Medula Espinal/crescimento & desenvolvimento
Medula Espinal/patologia
Proteína 1 de Sobrevivência do Neurônio Motor/metabolismo
Peixe-Zebra/genética
Peixe-Zebra/crescimento & desenvolvimento
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Survival of Motor Neuron 1 Protein); 0 (smn1 protein, zebrafish); 8L5014XET7 (Terazosin); 8L70Q75FXE (Adenosine Triphosphate); EC 2.7.2.3 (Pgk1 protein, mouse); EC 2.7.2.3 (Phosphoglycerate Kinase); XM03YJ541D (Prazosin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170809
[Lr] Data última revisão:
170809
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pgen.1006744


  7 / 2216 MEDLINE  
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[PMID]:28423608
[Au] Autor:Pang Y; Yang C; Schovanek J; Wang H; Bullova P; Caisova V; Gupta G; Wolf KI; Semenza GL; Zhuang Z; Pacak K
[Ad] Endereço:Section on Medical Neuroendocrinology, Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland, USA.
[Ti] Título:Anthracyclines suppress pheochromocytoma cell characteristics, including metastasis, through inhibition of the hypoxia signaling pathway.
[So] Source:Oncotarget;8(14):22313-22324, 2017 Apr 04.
[Is] ISSN:1949-2553
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, neuroendocrine tumors derived from adrenal or extra-adrenal chromaffin cells, respectively. Metastases are discovered in 3-36% of patients at the time of diagnosis. Currently, only suboptimal treatment options exist. Therefore, new therapeutic compounds targeting metastatic PHEOs/PGLs are urgently needed. Here, we investigated if anthracyclines were able to suppress the progression of metastatic PHEO. We explored their effects on experimental mouse PHEO tumor cells using in vitro and in vivo models, and demonstrated that anthracyclines, particularly idarubicin (IDA), suppressed hypoxia signaling by preventing the binding of hypoxia-inducible factor 1 and 2 (HIF-1 and HIF-2) to the hypoxia response element (HRE) sites on DNA. This resulted in reduced transcriptional activation of HIF target genes, including erythropoietin (EPO), phosphoglycerate kinase 1 (PGK1), endothelin 1 (EDN1), glucose transporter 1 (GLUT1), lactate dehydrogenase A (LDHA), and vascular endothelial growth factor (VEGFA), which consequently inhibited the growth of metastatic PHEO. Additionally, IDA downregulated hypoxia signaling by interfering with the transcriptional activation of HIF1A and HIF2A. Furthermore, our animal model demonstrated the dose-dependent suppressive effect of IDA on metastatic PHEO growth in vivo. Our results indicate that anthracyclines are prospective candidates for inclusion in metastatic PHEO/PGL therapy, especially in patients with gene mutations involved in the hypoxia signaling pathway.
[Mh] Termos MeSH primário: Neoplasias das Glândulas Suprarrenais/tratamento farmacológico
Antineoplásicos/uso terapêutico
Hipóxia/tratamento farmacológico
Idarubicina/uso terapêutico
Feocromocitoma/tratamento farmacológico
[Mh] Termos MeSH secundário: Neoplasias das Glândulas Suprarrenais/patologia
Animais
Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo
Processos de Crescimento Celular/efeitos dos fármacos
Linhagem Celular Tumoral
Endotelina-1/genética
Endotelina-1/metabolismo
Eritropoetina/genética
Eritropoetina/metabolismo
Seres Humanos
Hipóxia/patologia
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Camundongos
Camundongos Nus
Metástase Neoplásica
Feocromocitoma/patologia
Fosfoglicerato Quinase/genética
Fosfoglicerato Quinase/metabolismo
Ligação Proteica
Transdução de Sinais/efeitos dos fármacos
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Basic Helix-Loop-Helix Transcription Factors); 0 (Endothelin-1); 0 (Hif1a protein, mouse); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (endothelial PAS domain-containing protein 1); 11096-26-7 (Erythropoietin); EC 2.7.2.3 (Pgk1 protein, mouse); EC 2.7.2.3 (Phosphoglycerate Kinase); ZRP63D75JW (Idarubicin)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170915
[Lr] Data última revisão:
170915
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170421
[St] Status:MEDLINE
[do] DOI:10.18632/oncotarget.16224


  8 / 2216 MEDLINE  
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[PMID]:28391351
[Au] Autor:Cao H; Yu H; Feng Y; Chen L; Liang F
[Ad] Endereço:Surgical Department I (Urology Department), Shanghai University of Traditional Chinese Medicine Affiliated LONGHUA Hospital, No. 725 Wanping Road South, Xuhui District, Shanghai, 200032, China.
[Ti] Título:Curcumin inhibits prostate cancer by targeting PGK1 in the FOXD3/miR-143 axis.
[So] Source:Cancer Chemother Pharmacol;79(5):985-994, 2017 May.
[Is] ISSN:1432-0843
[Cp] País de publicação:Germany
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Curcumin is a potent antitumor agent. The objective of this study was to explore the interaction between curcumin and PGK1, an oncogene in the FOXD3/miR-143 axis, in prostate cancer therapy. METHODS: MiRNA microarray analysis was used to identify miRNAs upregulated by curcumin treatment. MiR-143 was dramatically upregulated by curcumin. Cells were treated with antimiR-143 in combination to curcumin, followed by examining cell viability and migration. Bioinformatics analysis was used to investigate target genes of miR-143. The interaction between miR-143 and PGK1 was evaluated with dual-luciferase assay. Since FOXD3 is important in the regulation of miR-143, we explored whether curcumin regulated FOXD3 expression. FOXD3 was also ectopically overexpressed to investigate its effects on curcumin's regulation of miR-143. RESULTS: Curcumin treatment significantly upregulated miR-143 and decreased prostate cancer cell proliferation and migration. Those effects were attenuated by anti-miR-143 transfection. Both miR-143 overexpression and curcumin treatment inhibited PGK1 expression and ectopic expression of PGK1 antagonized curcumin's antitumor effects. FOXD3 was upregulated by miR-143. Ectopic expression of FOXD3 synergized with curcumin in upregulating miR-143 expression. CONCLUSION: Curcumin inhibits prostate cancer by upregulating miR-143. PGK1 is downregulated by miR-143, and FOXD3 upregulation is essential for the antitumor effect of curcumin.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Curcumina/farmacologia
Fatores de Transcrição Forkhead/efeitos dos fármacos
MicroRNAs/efeitos dos fármacos
Fosfoglicerato Quinase/efeitos dos fármacos
Neoplasias da Próstata/tratamento farmacológico
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Movimento Celular/efeitos dos fármacos
Sobrevivência Celular/efeitos dos fármacos
Biologia Computacional
Fatores de Transcrição Forkhead/biossíntese
Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos
Técnicas de Transferência de Genes
Seres Humanos
Lentivirus/genética
Masculino
MicroRNAs/biossíntese
Análise em Microsséries
Fosfoglicerato Quinase/biossíntese
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (FOXD3 protein, human); 0 (Forkhead Transcription Factors); 0 (MIRN143 microRNA, human); 0 (MicroRNAs); EC 2.7.2.3 (PGK1 protein, human); EC 2.7.2.3 (Phosphoglycerate Kinase); IT942ZTH98 (Curcumin)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170613
[Lr] Data última revisão:
170613
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170410
[St] Status:MEDLINE
[do] DOI:10.1007/s00280-017-3301-1


  9 / 2216 MEDLINE  
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[PMID]:28263974
[Au] Autor:Wan W; Peng K; Li M; Qin L; Tong Z; Yan J; Shen B; Yu C
[Ad] Endereço:State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Biology, School of Life Sciences, Xiamen University, Xiamen, China.
[Ti] Título:Histone demethylase JMJD1A promotes urinary bladder cancer progression by enhancing glycolysis through coactivation of hypoxia inducible factor 1α.
[So] Source:Oncogene;36(27):3868-3877, 2017 Jul 06.
[Is] ISSN:1476-5594
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:High aerobic glycolysis not only provides energy to cancer cells, but also supports their anabolic growth. JMJD1A, a histone demethylase that specifically demethylates H3K9me1/2, is overexpressed in multiple cancers, including urinary bladder cancer (UBC). It is unclear whether JMJD1A could promote cancer cell growth through enhancing glycolysis. In this study, we found that downregulation of JMJD1A decreased UBC cell proliferation, colony formation and xenograft tumor growth. Knockdown of JMJD1A inhibited glycolysis by decreasing the expression of genes participated in glucose metabolism, including GLUT1, HK2, PGK1, PGM, LDHA and MCT4. Mechanistically, JMJD1A cooperated with hypoxia inducible factor 1α (HIF1α), an important transcription factor for glucose metabolism, to induce the glycolytic gene expression. JMJD1A was recruited to the promoter of glycolytic gene PGK1 to demethylate H3K9me2. However, the JMJD1A (H1120Y) mutant, which loses the demethylase activity, failed to cooperate with HIF1α to induce the glycolytic gene expression, and failed to demethylate H3K9me2 on PGK1 promoter, suggesting that the demethylase activity of JMJD1A is essential for its coactivation function for HIF1α. Inhibition of glycolysis through knocking down HIF1α or PGK1 decelerated JMJD1A-enhanced UBC cell growth. Consistent with these results, a positive correlation between JMJD1A and several key glycolytic genes in human UBC samples was established by analyzing a microarray-based gene expression profile. In conclusion, our study demonstrates that JMJD1A promotes UBC progression by enhancing glycolysis through coactivation of HIF1α, implicating that JMJD1A is a potential molecular target for UBC treatment.
[Mh] Termos MeSH primário: Glicólise
Histona Desmetilases com o Domínio Jumonji/fisiologia
Neoplasias da Bexiga Urinária/enzimologia
[Mh] Termos MeSH secundário: Animais
Linhagem Celular Tumoral
Proliferação Celular
Progressão da Doença
Regulação Neoplásica da Expressão Gênica
Doenças Genéticas Ligadas ao Cromossomo X/genética
Doenças Genéticas Ligadas ao Cromossomo X/metabolismo
Glucose/metabolismo
Seres Humanos
Subunidade alfa do Fator 1 Induzível por Hipóxia
Masculino
Erros Inatos do Metabolismo/genética
Erros Inatos do Metabolismo/metabolismo
Camundongos Nus
Transplante de Neoplasias
Fosfoglicerato Quinase/deficiência
Fosfoglicerato Quinase/genética
Fosfoglicerato Quinase/metabolismo
Regiões Promotoras Genéticas
Elementos de Resposta
Transcrição Genética
Ativação Transcricional
Neoplasias da Bexiga Urinária/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (HIF1A protein, human); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); EC 1.14.11.- (Jumonji Domain-Containing Histone Demethylases); EC 1.14.11.- (KDM3A protein, human); EC 2.7.2.3 (Phosphoglycerate Kinase); IY9XDZ35W2 (Glucose)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170307
[St] Status:MEDLINE
[do] DOI:10.1038/onc.2017.13


  10 / 2216 MEDLINE  
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[PMID]:28238651
[Au] Autor:Qian X; Li X; Cai Q; Zhang C; Yu Q; Jiang Y; Lee JH; Hawke D; Wang Y; Xia Y; Zheng Y; Jiang BH; Liu DX; Jiang T; Lu Z
[Ad] Endereço:Brain Tumor Center and Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
[Ti] Título:Phosphoglycerate Kinase 1 Phosphorylates Beclin1 to Induce Autophagy.
[So] Source:Mol Cell;65(5):917-931.e6, 2017 Mar 02.
[Is] ISSN:1097-4164
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Autophagy is crucial for maintaining cell homeostasis. However, the precise mechanism underlying autophagy initiation remains to be defined. Here, we demonstrate that glutamine deprivation and hypoxia result in inhibition of mTOR-mediated acetyl-transferase ARD1 S228 phosphorylation, leading to ARD1-dependent phosphoglycerate kinase 1 (PGK1) K388 acetylation and subsequent PGK1-mediated Beclin1 S30 phosphorylation. This phosphorylation enhances ATG14L-associated class III phosphatidylinositol 3-kinase VPS34 activity by increasing the binding of phosphatidylinositol to VPS34. ARD1-dependent PGK1 acetylation and PGK1-mediated Beclin1 S30 phosphorylation are required for glutamine deprivation- and hypoxia-induced autophagy and brain tumorigenesis. Furthermore, PGK1 K388 acetylation levels correlate with Beclin1 S30 phosphorylation levels and poor prognosis in glioblastoma patients. Our study unearths an important mechanism underlying cellular-stress-induced autophagy initiation in which the protein kinase activity of the metabolic enzyme PGK1 plays an instrumental role and reveals the significance of the mutual regulation of autophagy and cell metabolism in maintaining cell homeostasis.
[Mh] Termos MeSH primário: Autofagossomos/enzimologia
Autofagia
Beclina-1/metabolismo
Neoplasias Encefálicas/enzimologia
Glioblastoma/enzimologia
Fosfoglicerato Quinase/metabolismo
[Mh] Termos MeSH secundário: Acetilação
Animais
Autofagossomos/patologia
Beclina-1/genética
Neoplasias Encefálicas/genética
Neoplasias Encefálicas/patologia
Linhagem Celular Tumoral
Proliferação Celular
Classe III de Fosfatidilinositol 3-Quinases/genética
Classe III de Fosfatidilinositol 3-Quinases/metabolismo
Feminino
Glioblastoma/genética
Glioblastoma/patologia
Glutamina/deficiência
Células HEK293
Seres Humanos
Camundongos Nus
Acetiltransferase N-Terminal A/genética
Acetiltransferase N-Terminal A/metabolismo
Acetiltransferase N-Terminal E/genética
Acetiltransferase N-Terminal E/metabolismo
Fosfoglicerato Quinase/genética
Fosforilação
Ligação Proteica
Interferência de RNA
Transdução de Sinais
Serina-Treonina Quinases TOR/genética
Serina-Treonina Quinases TOR/metabolismo
Fatores de Tempo
Transfecção
Carga Tumoral
Hipóxia Tumoral
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (BECN1 protein, human); 0 (Beclin-1); 0RH81L854J (Glutamine); EC 2.3.1.88 (N-Terminal Acetyltransferase A); EC 2.3.1.88 (N-Terminal Acetyltransferase E); EC 2.3.1.88 (NAA10 protein, human); EC 2.7.1.1 (MTOR protein, human); EC 2.7.1.1 (TOR Serine-Threonine Kinases); EC 2.7.1.137 (Class III Phosphatidylinositol 3-Kinases); EC 2.7.2.3 (PGK1 protein, human); EC 2.7.2.3 (Phosphoglycerate Kinase)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171026
[Lr] Data última revisão:
171026
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170228
[St] Status:MEDLINE



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