Base de dados : MEDLINE
Pesquisa : D08.811.037.375 [Categoria DeCS]
Referências encontradas : 269 [refinar]
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[PMID]:29054757
[Au] Autor:Zhang K; Guo L
[Ad] Endereço:Department of Dermatology, Liaocheng City People's Hospital, Liaocheng City, Shandong Province 252000, People's Republic of China.
[Ti] Título:MiR-767 promoted cell proliferation in human melanoma by suppressing CYLD expression.
[So] Source:Gene;641:272-278, 2018 Jan 30.
[Is] ISSN:1879-0038
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:MicroRNAs (miRNAs) have emerged as critical regulators for cancer development and progression of human melanoma. However, the potential molecular mechanism of miR-767 in human melanoma has not been intensively investigated. In this present study, we confirmed that miR-767 was frequently up-regulated in human melanoma tissues and cell lines. Ectopic expression of miR-767 promoted cell proliferation in human melanoma cell lines A375 and WM35, whereas miR-767-in reversed the function. Bioinformatics analysis revealed that cylindromatosis (CYLD) was hypothesized to be a possible target gene of miR-767, and this was confirmed by luciferase activity assay. Knockdown of CYLD counteracted the proliferation arrest by miR-767-in in melanoma cells A375 and WM35. In conclusion, our study indicated that miR-767 acted as a role of tumor promoter by targeting CYLD in human melanoma, and might serve as a prognostic or therapeutic target for human melanoma.
[Mh] Termos MeSH primário: Proliferação Celular/genética
Enzima Desubiquitinante CYLD/genética
Melanoma/genética
Melanoma/patologia
MicroRNAs/genética
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Expressão Ectópica do Gene/genética
Seres Humanos
Regiões Promotoras Genéticas/genética
Regulação para Cima/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (MIRN-767 microRNA, human); 0 (MicroRNAs); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
[Em] Mês de entrada:1711
[Cu] Atualização por classe:171128
[Lr] Data última revisão:
171128
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:171022
[St] Status:MEDLINE


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[PMID]:28882891
[Au] Autor:Tanishima M; Takashima S; Honda A; Yasuda D; Tanikawa T; Ishii S; MaruYama T
[Ad] Endereço:From the Laboratory of Cell Recognition and Response, Department of Developmental Biology and Neurosciences, Graduate School of Life Sciences, Tohoku University, Sendai, Miyagi 980-8578, Japan.
[Ti] Título:Identification of optineurin as an interleukin-1 receptor-associated kinase 1-binding protein and its role in regulation of MyD88-dependent signaling.
[So] Source:J Biol Chem;292(42):17250-17257, 2017 Oct 20.
[Is] ISSN:1083-351X
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Upon stimulation of toll-like receptors with various microbial ligands, induction of a variety of inflammatory genes is elicited by activation of a myeloid differentiation primary-response protein 88 (MyD88)-dependent signaling pathway. Interleukin-1 (IL-1) receptor-associated kinase 1 (IRAK1) plays an essential role in this pathway by activating nuclear factor κB (NF-κB) and mitogen-activated kinases (MAPKs). Here, we identified optineurin (OPTN) as an IRAK1-binding protein by yeast two-hybrid screening using IRAK1 as bait. A C-terminal fragment of OPTN harboring a ubiquitin-binding domain was co-immunoprecipitated with IRAK1. In reporter analyses, overexpression of OPTN inhibited IL-1ß-, IRAK1-, and LPS-induced NF-κB activation. Consistently, OPTN deficiency resulted in increased NF-κB activation in response to IL-1ß/LPS stimulation. To address the mechanisms underlying the inhibitory effect of OPTN on NF-κB signaling, we focused on tumor necrosis factor (TNF) receptor-associated factor 6 (TRAF6), which is an adaptor protein of IRAK1 and upon polyubiquitination plays a crucial role during NF-κB activation. Overexpression of OPTN prevented TRAF6 polyubiquitination. Furthermore, OPTN H486R mutant, which is unable to recruit the deubiquitinase CYLD, failed to inhibit IRAK1-induced NF-κB activation. These results suggest that the IRAK1-binding protein OPTN negatively regulates IL-1ß/LPS-induced NF-κB activation by preventing polyubiquitination of TRAF6.
[Mh] Termos MeSH primário: Proteínas do Olho/metabolismo
Quinases Associadas a Receptores de Interleucina-1/metabolismo
Fator 88 de Diferenciação Mieloide/metabolismo
Transdução de Sinais/fisiologia
Fator de Transcrição TFIIIA/metabolismo
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Cisteína Endopeptidases/genética
Cisteína Endopeptidases/metabolismo
Enzima Desubiquitinante CYLD
Proteínas do Olho/genética
Células HEK293
Seres Humanos
Quinases Associadas a Receptores de Interleucina-1/genética
Lipopolissacarídeos/farmacologia
Camundongos
Mutação de Sentido Incorreto
Fator 88 de Diferenciação Mieloide/genética
NF-kappa B/genética
NF-kappa B/metabolismo
Células RAW 264.7
Transdução de Sinais/efeitos dos fármacos
Fator 6 Associado a Receptor de TNF/genética
Fator 6 Associado a Receptor de TNF/metabolismo
Fator de Transcrição TFIIIA/genética
Proteínas Supressoras de Tumor/genética
Proteínas Supressoras de Tumor/metabolismo
Ubiquitinação/efeitos dos fármacos
Ubiquitinação/fisiologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Eye Proteins); 0 (Lipopolysaccharides); 0 (MYD88 protein, human); 0 (Myd88 protein, mouse); 0 (Myeloid Differentiation Factor 88); 0 (NF-kappa B); 0 (OPTN protein, human); 0 (Optn protein, mouse); 0 (TNF Receptor-Associated Factor 6); 0 (Tifab protein, human); 0 (Transcription Factor TFIIIA); 0 (Tumor Suppressor Proteins); EC 2.7.11.1 (IRAK1 protein, human); EC 2.7.11.1 (Interleukin-1 Receptor-Associated Kinases); EC 2.7.11.1 (Irak1 protein, mouse); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (CYLD protein, mouse); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD); EC 3.4.22.- (Cysteine Endopeptidases)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170909
[St] Status:MEDLINE
[do] DOI:10.1074/jbc.M117.813899


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[PMID]:28731516
[Au] Autor:Su XW; Lu G; Leung CK; Liu Q; Li Y; Tsang KS; Zhao SD; Chan DTM; Kung HF; Poon WS
[Ad] Endereço:Division of Neurosurgery, Department of Surgery, Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China.
[Ti] Título:miR-181d regulates human dendritic cell maturation through NF-κB pathway.
[So] Source:Cell Prolif;50(5), 2017 Oct.
[Is] ISSN:1365-2184
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:OBJECTIVES: MicroRNAs (miRNAs) are considered as the cellular regulators which post-transcriptionally modulate gene expression in diverse biological processes including cell development and immunity. In this study, we investigated functions of miR-181d in dendritic cells (DCs) maturation, and the underlying mechanisms were also explored. MATERIALS AND METHODS: Here we did the miRNA screening in human DCs in response to lipopolysaccharides (LPS) by quantitative real-time PCR (qRT-PCR). The expressions of DCs maturation markers were measured after miRNA mimics transfections. The pharmacological inhibitors of signalling pathways were applied to examine miR-181d effect on DCs maturation by Western blot. Luciferase assay and mixed lymphocyte reaction (MLR) were also performed to reveal the target gene of miR-181d and test the viability of T cells treated with miR-181d transfected DCs. RESULTS: Overexpression of miR-181d per se is sufficient to promote DCs maturation, and up-regulate CD80 and CD83 expressions without LPS. Besides, we showed that miR-181d activated NF-κB pathway and also promoted the expression of pro-inflammatory cytokine IL12 and TNF-α. Inhibition of NF-κB pathway suppressed DCs maturation. Luciferase reporter assay and target gene knockdown assay indicated that miR-181d targets regulator cylindromatosis (CYLD), a primary negative regulator of NF-κB pathway. MLR assay showed that miR-181d-transfected DCs could promote T-cell proliferation than iDCs in vitro. CONCLUSION: Our study demonstrates that miR-181d is required for DCs maturation through the activation of NF-κB pathway by targeting CYLD.
[Mh] Termos MeSH primário: Células Dendríticas/citologia
Lipopolissacarídeos/imunologia
MicroRNAs/genética
NF-kappa B/imunologia
Transdução de Sinais
Regulação para Cima
[Mh] Termos MeSH secundário: Diferenciação Celular
Proliferação Celular
Células Cultivadas
Células Dendríticas/imunologia
Células Dendríticas/metabolismo
Enzima Desubiquitinante CYLD
Seres Humanos
Interleucina-12/imunologia
MicroRNAs/imunologia
Monócitos/citologia
Monócitos/imunologia
Monócitos/metabolismo
Fator de Necrose Tumoral alfa/imunologia
Proteínas Supressoras de Tumor/genética
Proteínas Supressoras de Tumor/imunologia
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipopolysaccharides); 0 (MIrn181 microRNA, human); 0 (MicroRNAs); 0 (NF-kappa B); 0 (Tumor Necrosis Factor-alpha); 0 (Tumor Suppressor Proteins); 187348-17-0 (Interleukin-12); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170722
[St] Status:MEDLINE
[do] DOI:10.1111/cpr.12358


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[PMID]:28668838
[Au] Autor:Orfanidou T; Xanthopoulos K; Dafou D; Pseftogas A; Hadweh P; Psyllaki C; Hatzivassiliou E; Mosialos G
[Ad] Endereço:School of Biology, Aristotle University of Thessaloniki, Thessaloniki, Greece.
[Ti] Título:Down-regulation of the Tumor Suppressor CYLD Enhances the Transformed Phenotype of Human Breast Cancer Cells.
[So] Source:Anticancer Res;37(7):3493-3503, 2017 07.
[Is] ISSN:1791-7530
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:BACKGROUND/AIM: The cylindromatosis tumor suppressor (CYLD) has been implicated in the inhibition of human breast cancer development by virtue of the poor prognosis of patients with down-regulated CYLD expression. In order to investigate the mechanism of breast cancer suppression by CYLD, in the present study, cellular and molecular aspects of CYLD-dependent phenotypic regulation of different types of human breast cancer cell lines were analyzed. MATERIALS AND METHODS: CYLD expression was down-regulated by RNA interference in human breast cancer cell lines. Parental and CYLD-deficient cell lines were evaluated for their viability, migratory capacity, anchorage-independent growth and chemoresistance. Wild-type and mutated forms of CYLD were also evaluated for their ability to suppress the clonogenic potential of breast cancer cells. RESULTS: CYLD down-regulation enhanced the survival and migratory properties of basal and luminal breast cancer cell lines. In addition, down-regulation of CYLD expression enhanced the ability of human breast cancer cells to grow in an anchorage-independent manner and could be associated with resistance to chemotherapeutic drugs. The growth-suppressive properties of CYLD on breast cancer cell lines were dependent on its de-ubiquitinating activity and its amino terminal cytoskeleton-interacting region. CONCLUSION: Our results establish a broad range of tumor-suppressive properties that are conferred by CYLD in basal and luminal human breast cancer cells and support the significance of targeted de-ubiquitination by CYLD in breast cancer cell growth suppression.
[Mh] Termos MeSH primário: Neoplasias da Mama/genética
Regulação para Baixo/genética
Genes Supressores de Tumor/fisiologia
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Linhagem Celular
Linhagem Celular Tumoral
Movimento Celular/genética
Sobrevivência Celular/genética
Citoesqueleto/genética
Enzima Desubiquitinante CYLD
Resistência a Medicamentos Antineoplásicos/genética
Feminino
Células HEK293
Seres Humanos
Células MCF-7
Interferência de RNA/fisiologia
Ubiquitinação/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Tumor Suppressor Proteins); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170703
[St] Status:MEDLINE


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[PMID]:28582447
[Au] Autor:Sim MY; Huynh H; Go ML; Yuen JSP
[Ad] Endereço:Department of Urology, Singapore General Hospital, Republic of Singapore.
[Ti] Título:Action of YM155 on clear cell renal cell carcinoma does not depend on survivin expression levels.
[So] Source:PLoS One;12(6):e0178168, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The dioxonapthoimidazolium YM155 is a survivin suppressant which has been investigated as an anticancer agent in clinical trials. Here, we investigated its growth inhibitory properties on a panel of immortalized and patient derived renal cell carcinoma (RCC) cell lines which were either deficient in the tumour suppressor von Hippel-Lindau (VHL) protein or possessed a functional copy. Neither the VHL status nor the survivin expression levels of these cell lines influenced their susceptibility to growth inhibition by YM155. Of the various RCC lines, the papillary subtype was more resistant to YM155, suggesting that the therapeutic efficacy of YM155 may be restricted to clear cell subtypes. YM155 was equally potent in cells (RCC786.0) in which survivin expression had been stably silenced or overexpressed, implicating a limited reliance on survivin in the mode of action of YM155. A follow-up in-vitro high throughput RNA microarray identified possible targets of YM155 apart from survivin. Selected genes (ID1, FOXO1, CYLD) that were differentially expressed in YM155-sensitive RCC cells and relevant to RCC pathology were validated with real-time PCR and western immunoblotting analyses. Thus, there is corroboratory evidence that the growth inhibitory activity of YM155 in RCC cell lines is not exclusively mediated by its suppression of survivin. In view of the growing importance of combination therapy in oncology, we showed that a combination of YM155 and sorafenib at ½ x IC50 concentrations was synergistic on RCC786.0 cells. However, when tested intraperitoneally on a murine xenograft model derived from a nephrectomised patient with clear cell RCC, a combination of suboptimal doses of both drugs failed to arrest tumour progression. The absence of synergy in vivo highlighted the need to further optimize the dosing schedules of YM155 and sorafenib, as well as their routes of administration. It also implied that the expression of other oncogenic proteins which YM155 may target is either low or absent in this clear cell RCC.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carcinoma de Células Renais/tratamento farmacológico
Imidazóis/farmacologia
Proteínas Inibidoras de Apoptose/genética
Neoplasias Renais/tratamento farmacológico
Naftoquinonas/farmacologia
Niacinamida/análogos & derivados
Compostos de Fenilureia/farmacologia
Proteína Supressora de Tumor Von Hippel-Lindau/genética
[Mh] Termos MeSH secundário: Animais
Carcinoma de Células Renais/genética
Carcinoma de Células Renais/metabolismo
Carcinoma de Células Renais/patologia
Linhagem Celular Tumoral
Sobrevivência Celular/efeitos dos fármacos
Enzima Desubiquitinante CYLD
Relação Dose-Resposta a Droga
Combinação de Medicamentos
Proteína Forkhead Box O1/genética
Proteína Forkhead Box O1/metabolismo
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Proteínas Inibidoras de Apoptose/antagonistas & inibidores
Proteínas Inibidoras de Apoptose/metabolismo
Proteína 1 Inibidora de Diferenciação/genética
Proteína 1 Inibidora de Diferenciação/metabolismo
Neoplasias Renais/genética
Neoplasias Renais/metabolismo
Neoplasias Renais/patologia
Masculino
Camundongos
Camundongos SCID
Niacinamida/farmacologia
Cultura Primária de Células
Transdução de Sinais
Proteínas Supressoras de Tumor/genética
Proteínas Supressoras de Tumor/metabolismo
Proteína Supressora de Tumor Von Hippel-Lindau/antagonistas & inibidores
Proteína Supressora de Tumor Von Hippel-Lindau/metabolismo
Ensaios Antitumorais Modelo de Xenoenxerto
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (BIRC5 protein, human); 0 (Drug Combinations); 0 (FOXO1 protein, human); 0 (Forkhead Box Protein O1); 0 (ID1 protein, human); 0 (Imidazoles); 0 (Inhibitor of Apoptosis Proteins); 0 (Inhibitor of Differentiation Protein 1); 0 (Naphthoquinones); 0 (Phenylurea Compounds); 0 (Tumor Suppressor Proteins); 0 (YM 155); 25X51I8RD4 (Niacinamide); 9ZOQ3TZI87 (sorafenib); EC 2.3.2.27 (Von Hippel-Lindau Tumor Suppressor Protein); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD); EC 6.3.2.- (VHL protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170606
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178168


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[PMID]:28542437
[Au] Autor:Takeda H; Zhou W; Kido K; Suno R; Iwasaki T; Kobayashi T; Sawasaki T
[Ad] Endereço:Proteo-Science Center, Ehime University, Matsuyama, Ehime, Japan.
[Ti] Título:CP5 system, for simple and highly efficient protein purification with a C-terminal designed mini tag.
[So] Source:PLoS One;12(5):e0178246, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:There are many strategies to purify recombinant proteins of interest, and affinity purification utilizing monoclonal antibody that targets a linear epitope sequence is one of the essential techniques used in current biochemistry and structural biology. Here we introduce a new protein purification system using a very short CP5 tag. First, we selected anti-dopamine receptor D1 (DRD1) rabbit monoclonal antibody clone Ra62 (Ra62 antibody) as capture antibody, and identified its minimal epitope sequence as a 5-amino-acid sequence at C-terminal of DRD1 (GQHPT-COOH, D1CE sequence). We found that single amino acid substitution in D1CE sequence (GQHVT-COOH) increased dissociation rate up to 10-fold, and named the designed epitope sequence CP5 tag. Using Ra62 antibody and 2 peptides with different affinity, we developed a new affinity protein purification method, CP5 system. Ra62 antibody quickly captures CP5-tagged target protein, and captured CP5-tagged protein was eluted by competing with higher affinity D1CE peptide. By taking the difference of the affinity between D1CE and CP5, sharp elution under mild condition was achieved. Using CP5 system, we successfully purified deubiquitinase CYLD and E3 ubiquitin ligase MARCH3, and detected their catalytic activity. As to G protein-coupled receptors (GPCRs), 9 out of 12 cell-free synthesized ones were purified, demonstrating its purification capability of integral membrane proteins. CP5 tagged CHRM2 expressed by baculovirus-insect cell was also successfully purified by CP5 system. CP5 system offers several distinct advantages in addition to its specificity and elution performance. CP5 tag is easy to construct and handle because of its short length, which has less effect on protein characters. Mild elution of CP5 system is particulaly suitable for preparing delicate proteins such as enzymes and membrane proteins. Our data demonstrate that CP5 system provides a new promising option in protein sample preparation with high yield, purity and activity for downstream applications in functional and structural analysis.
[Mh] Termos MeSH primário: Cromatografia de Afinidade/métodos
Proteínas Recombinantes/isolamento & purificação
[Mh] Termos MeSH secundário: Substituição de Aminoácidos
Animais
Anticorpos Monoclonais/imunologia
Células CHO
Proteínas de Transporte/isolamento & purificação
Proteínas de Transporte/metabolismo
Sistema Livre de Células
Cricetulus
Enzima Desubiquitinante CYLD
Epitopos/genética
Epitopos/imunologia
Células HEK293
Células HeLa
Seres Humanos
Immunoblotting
Células MCF-7
Proteínas de Membrana/isolamento & purificação
Proteínas de Membrana/metabolismo
Coelhos
Receptores de Dopamina D1/genética
Receptores de Dopamina D1/imunologia
Sitios de Sequências Rotuladas
Proteínas Supressoras de Tumor/isolamento & purificação
Proteínas Supressoras de Tumor/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antibodies, Monoclonal); 0 (Carrier Proteins); 0 (Epitopes); 0 (Membrane Proteins); 0 (Receptors, Dopamine D1); 0 (Recombinant Proteins); 0 (Tumor Suppressor Proteins); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD); EC 6.3.2.19 (MARCH2 protein, human)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170526
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0178246


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[PMID]:28295222
[Au] Autor:Hajek M; Sewell A; Kaech S; Burtness B; Yarbrough WG; Issaeva N
[Ad] Endereço:Division of Otolaryngology, Department of Surgery, Yale University, New Haven, Connecticut.
[Ti] Título:TRAF3/CYLD mutations identify a distinct subset of human papillomavirus-associated head and neck squamous cell carcinoma.
[So] Source:Cancer;123(10):1778-1790, 2017 May 15.
[Is] ISSN:1097-0142
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:BACKGROUND: The incidence of human papillomavirus (HPV)-associated (HPV-positive) head and neck squamous cell carcinoma (HNSCC) of the oropharynx has dramatically increased over the last decade and continues to rise. Newly diagnosed HPV-positive HNSCCs in the United States currently outnumber any other HPV-associated cancers, including cervical cancer. Despite introduction of the HPV vaccine, the epidemic of HPV-positive HNSCC is expected to continue for approximately 60 years. Compared with patients who have tobacco-associated HNSCC, those who have HPV-positive HNSCC have better overall survival and response to treatment. Current treatment, including chemotherapy and radiation therapy, is associated with lifelong morbidity, and there are limited treatments and no curative options for patients who develop recurrent metastatic disease. Therapeutic de-escalation (decreased radiation dose) is being tested through clinical trials; however, those studies select patients based solely on tumor and patient smoking characteristics. Mechanisms of HPV-driven carcinogenesis in HNSCC are not well understood, which limits new therapeutic strategies and hinders the appropriate selection of patients for de-escalation therapy. METHODS: The authors analyzed HNSCC data from The Cancer Genome Atlas to identify molecular characteristics that correlate with outcomes and integration status of the HPV genome. RESULTS: The current investigations identified a subset of HPV-positive HNSCCs with mutations in the genes TRAF3 (tumor necrosis factor receptor-associated factor 3) and CYLD (cylindromatosis lysine 63 deubiquitinase). Defects in TRAF3 and CYLD correlated with the activation of transcriptional factor nuclear factor κB, episomal HPV status of tumors, and improved patient survival. CONCLUSIONS: Defects in TRAF3/CYLD were accompanied with the activation of nuclear factor κB signaling and maintenance of episomal HPV in tumors, suggesting that these mutations may support an alternative mechanism of HPV tumorigenesis in head and neck tumors. Cancer 2017;123:1778-1790. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.
[Mh] Termos MeSH primário: Carcinoma de Células Escamosas/genética
Neoplasias de Cabeça e Pescoço/genética
Neoplasias Orofaríngeas/genética
Infecções por Papillomavirus/genética
Fator 3 Associado a Receptor de TNF/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Carcinoma de Células Escamosas/complicações
Carcinoma de Células Escamosas/metabolismo
Carcinoma de Células Escamosas/virologia
Bases de Dados Factuais
Enzima Desubiquitinante CYLD
Neoplasias de Cabeça e Pescoço/complicações
Neoplasias de Cabeça e Pescoço/metabolismo
Neoplasias de Cabeça e Pescoço/virologia
Seres Humanos
NF-kappa B/metabolismo
Neoplasias Orofaríngeas/complicações
Neoplasias Orofaríngeas/metabolismo
Neoplasias Orofaríngeas/virologia
Papillomaviridae
Infecções por Papillomavirus/complicações
Infecções por Papillomavirus/metabolismo
Prognóstico
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (NF-kappa B); 0 (TNF Receptor-Associated Factor 3); 0 (TRAF3 protein, human); 0 (Tumor Suppressor Proteins); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:AIM; IM
[Da] Data de entrada para processamento:170316
[St] Status:MEDLINE
[do] DOI:10.1002/cncr.30570


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[PMID]:28250134
[Au] Autor:Huang J; Zhu L; Qiu C; Xu X; Zhang L; Ding X; Liao Q; Xu J; Zhang X
[Ad] Endereço:Shanghai Public Health Clinical Center & Institutes of Biomedical Sciences, Shanghai Medical College, Fudan University, Shanghai, China.
[Ti] Título:MicroRNA miR-126-5p Enhances the Inflammatory Responses of Monocytes to Lipopolysaccharide Stimulation by Suppressing Cylindromatosis in Chronic HIV-1 Infection.
[So] Source:J Virol;91(10), 2017 May 15.
[Is] ISSN:1098-5514
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Persistent immune activation during chronic human immunodeficiency virus type 1 (HIV-1) infection facilitates immune dysfunction and thereby fuels disease progression. The translocation of bacterial derivatives into blood and the hyperinflammatory responsiveness of monocytes have been considered important causative factors for persistent immune activation. Whether microRNAs (miRNAs) are involved in regulating monocyte-mediated inflammatory responses during chronic HIV-1 infection remains elusive. In this study, we show that miR-126-5p functions as a positive regulator of monocyte-mediated inflammatory responses. Significantly increased miRNA miR-126-5p and decreased cylindromatosis (CYLD) were observed in primary monocytes from chronic HIV-1 patients. Inhibition of miR-126-5p in monocytes from chronic HIV-1 patients attenuated the responsiveness of these cells to lipopolysaccharide (LPS) stimulation. Gain-of-function assays confirmed that miR-126-5p could downregulate CYLD, which in turn caused an upregulation of phosphorylation of JNK protein (pJNK) and enhanced inflammatory responses of monocytes to LPS stimulation. Overall, miR-126-5p upregulates the responsiveness of monocytes to LPS stimulation in chronic HIV-1 infection, and the suppression of miR-126-5p and the promotion of CYLD expression in primary monocytes may represent a practical immune intervention strategy to contain persistent inflammation in chronic HIV-1 infection. Monocyte-mediated hyperinflammatory responses during chronic HIV-1 infection are important causative factors driving AIDS progression; however, the underlying mechanism has not been fully addressed. We demonstrated that miR-126-5p, one of the most upregulated miRNAs during chronic HIV-1 infection, could enhance the inflammatory responses of monocytes to LPS by suppressing the inhibitory protein CYLD and thereby unleashing the expression of pJNK in the LPS/Toll-like receptor 4/mitogen-activated protein kinase pathway. This observation reveals a new mechanism for HIV-1 pathogenesis, which could be targeted by immune intervention.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica
Infecções por HIV/imunologia
Lipopolissacarídeos/imunologia
MicroRNAs/genética
MicroRNAs/imunologia
Monócitos/imunologia
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Doença Crônica
Enzima Desubiquitinante CYLD
Regulação para Baixo
Seres Humanos
Inflamação
Sistema de Sinalização das MAP Quinases
Proteínas Supressoras de Tumor/metabolismo
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Lipopolysaccharides); 0 (MIRN126 microRNA, human); 0 (MicroRNAs); 0 (Tumor Suppressor Proteins); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170303
[St] Status:MEDLINE


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[PMID]:28184924
[Au] Autor:Liu J; Su Z; Zeng Y; Zhang H; Yang S; Liu G
[Ad] Endereço:Department of Hepato-Biliary-Pancreatic Surgery, Sun Yat-sen Memorial Hospital, Sun Yat­sen University, Guangzhou, Guangdong 510120, P.R. China.
[Ti] Título:miR-922 regulates CYLD expression and promotes the cell proliferation of human hepatocellular carcinoma.
[So] Source:Oncol Rep;37(3):1445-1450, 2017 Mar.
[Is] ISSN:1791-2431
[Cp] País de publicação:Greece
[La] Idioma:eng
[Ab] Resumo:Evidence reveals that microRNAs (miRNAs) play essential roles in hepatocellular carcinoma (HCC) tumorigenesis. In the present study, we identified an essential role for miR-922 in the development of HCC. We found that miR-922 was significantly upregulated in HCC cells and clinical tissues. Gain and loss of function studies indicated that miR-922 significantly promoted HCC cell proliferation. We subsequently identified that cylindromatosis (CYLD) was a target gene of miR-922. Moreover, miR-922 decreased CYLD expression, subsequently upregulating the expression of c-Myc and cyclin D1, while downregulating p-Rb expression. Furthermore, knockdown of CYLD expression by siRNA partially counteracted the tumor suppressive effect of the inhibitor of miR­922, miR­922-in. Taken together, our findings indicate that miR-922 plays a key role in the promotion of HCC cell proliferation, and strongly suggest that exogenous miR-922 may have therapeutic value for treating HCC.
[Mh] Termos MeSH primário: Biomarcadores Tumorais/metabolismo
Carcinoma Hepatocelular/patologia
Proliferação Celular
Neoplasias Hepáticas/patologia
MicroRNAs/genética
Proteínas Supressoras de Tumor/metabolismo
[Mh] Termos MeSH secundário: Apoptose
Biomarcadores Tumorais/genética
Western Blotting
Carcinoma Hepatocelular/genética
Carcinoma Hepatocelular/metabolismo
Adesão Celular
Enzima Desubiquitinante CYLD
Seres Humanos
Fígado/metabolismo
Fígado/patologia
Neoplasias Hepáticas/genética
Neoplasias Hepáticas/metabolismo
Estadiamento de Neoplasias
Prognóstico
RNA Mensageiro/genética
Reação em Cadeia da Polimerase em Tempo Real
Reação em Cadeia da Polimerase Via Transcriptase Reversa
Células Tumorais Cultivadas
Proteínas Supressoras de Tumor/genética
[Pt] Tipo de publicação:COMPARATIVE STUDY; JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Biomarkers, Tumor); 0 (MIRN922 microRNA, human); 0 (MicroRNAs); 0 (RNA, Messenger); 0 (Tumor Suppressor Proteins); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170211
[St] Status:MEDLINE
[do] DOI:10.3892/or.2017.5431


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[PMID]:27890238
[Au] Autor:Dubois A; Hodgson K; Rajan N
[Ad] Endereço:Department of Dermatology, Royal Victoria Infirmary, Queen Victoria Road, Newcastle upon Tyne NE1 4LP, UK.
[Ti] Título:Understanding Inherited Cylindromas: Clinical Implications of Gene Discovery.
[So] Source:Dermatol Clin;35(1):61-71, 2017 Jan.
[Is] ISSN:1558-0520
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Cylindromas are cutaneous tumors first described in the medical literature over 150 years ago. They are now known to occur on an inherited basis as a result of mutations in the tumor-suppressor gene CYLD. The discovery of this gene has provided novel insights into this rare skin tumor syndrome. As well as enabling genetic counseling of affected patients, the knowledge of CYLD function has led to steps toward development of novel therapeutics, with CYLD-regulated signaling pathways as the target for this approach.
[Mh] Termos MeSH primário: Síndromes Neoplásicas Hereditárias/genética
Neoplasias Cutâneas/genética
Proteínas Supressoras de Tumor/genética
[Mh] Termos MeSH secundário: Enzima Desubiquitinante CYLD
Genótipo
Seres Humanos
Mutação
Síndromes Neoplásicas Hereditárias/patologia
Fenótipo
Neoplasias Cutâneas/patologia
[Pt] Tipo de publicação:JOURNAL ARTICLE; REVIEW
[Nm] Nome de substância:
0 (Tumor Suppressor Proteins); EC 3.4.19.12 (CYLD protein, human); EC 3.4.19.12 (Deubiquitinating Enzyme CYLD)
[Em] Mês de entrada:1704
[Cu] Atualização por classe:171116
[Lr] Data última revisão:
171116
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161129
[St] Status:MEDLINE



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