Base de dados : MEDLINE
Pesquisa : D08.811.277.040.330.300.400.700.300 [Categoria DeCS]
Referências encontradas : 471 [refinar]
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[PMID]:28881218
[Au] Autor:Zhang N; Fu L; Bu Y; Yao Y; Wang Y
[Ad] Endereço:Department of Blood Transfusion, The Second Xiangya Hospital of Central South University, 139 Ren Min Zhong Road, Changsha 410011, China.
[Ti] Título:Downregulated expression of miR-223 promotes Toll-like receptor-activated inflammatory responses in macrophages by targeting RhoB.
[So] Source:Mol Immunol;91:42-48, 2017 11.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Toll-like receptors (TLRs) induced-inflammatory response must be tightly regulated to avoid impairment in host itself. Numerous factors have been identified in regulation of TLR-triggered inflammatory response. Among these, microRNAs (miRNAs) are small non-coding RNA molecules which have got much attention. MiR-223, which highly expresses in myeloid cells of the bone marrow, has reported to participate in kinds of inflammatory responses by targeting inflammasome sensor-NLRP3 to repress production of IL-6 and IL-1ß, and thus attenuate inflammatory response. However, the function of miR-223 in TLRs-activated inflammatory response of macrophages is not clear. Here we found miR-223 expression is dramatically reduced in macrophages by TLR ligand stimulation (e.g. LPS, CpG and poly (I:C)). The down-regulated miR-223 leads to the increase in the RhoB expression, which induce the activation of NF-κB and MAPK signaling, promoting TNF-α, IL-6 and IL-1ß production upon LPS stimulation. In addition, the histone deacetylase inhibitor trichostatin A increased miR-223 expression obviously in TLR-triggered macrophages, which in turn suppressed RhoB expression and downstream IL-6 production, suggesting that the inhibition of miR-223 by histone deacetylation may be involved in the regulation of TLR-activated inflammatory response. Herein, our findings suggest that miR-223-RhoB axis might be a novel target for the treatment of inflammatory diseases.
[Mh] Termos MeSH primário: Regulação da Expressão Gênica/imunologia
Macrófagos/imunologia
MicroRNAs/imunologia
Receptores Toll-Like/imunologia
Proteína rhoB de Ligação ao GTP/imunologia
[Mh] Termos MeSH secundário: Animais
Regulação da Expressão Gênica/genética
Inflamação/genética
Inflamação/imunologia
Inflamação/patologia
Interleucina-1beta/genética
Interleucina-1beta/imunologia
Interleucina-6/genética
Interleucina-6/imunologia
Macrófagos/patologia
Camundongos
MicroRNAs/genética
Proteína 3 que Contém Domínio de Pirina da Família NLR/genética
Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia
Células RAW 264.7
Receptores Toll-Like/genética
Proteína rhoB de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T
[Nm] Nome de substância:
0 (IL1B protein, mouse); 0 (Interleukin-1beta); 0 (Interleukin-6); 0 (MIRN223 microRNA, mouse); 0 (MicroRNAs); 0 (NLR Family, Pyrin Domain-Containing 3 Protein); 0 (Nlrp3 protein, mouse); 0 (Toll-Like Receptors); 0 (interleukin-6, mouse); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171120
[Lr] Data última revisão:
171120
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170908
[St] Status:MEDLINE


  2 / 471 MEDLINE  
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[PMID]:28739254
[Au] Autor:Nomikou E; Stournaras C; Kardassis D
[Ad] Endereço:Laboratory of Biochemistry, Division of Basic Medical Sciences, University of Crete Medical School, Heraklion 71003, Greece.
[Ti] Título:Functional analysis of the promoters of the small GTPases RhoA and RhoB in embryonic stem cells.
[So] Source:Biochem Biophys Res Commun;491(3):754-759, 2017 Sep 23.
[Is] ISSN:1090-2104
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Small GTPases of the Rho subfamily have been implicated in many physiological and pathological processes in various cell types including embryonic stem cells (ESCs). In the present study we performed a functional analysis of the promoters of the RhoA and the RhoB genes in order to identify regulatory elements that are important for their transcriptional control in ESCs. We show that RhoA mRNA levels were significantly higher compared with the RhoB mRNA levels in ESCs as well in various cancer cell lines and this difference could be accounted for by differences in the activities of the corresponding promoters. Deletion analysis of the RhoA and RhoB promoters in ESCs revealed that the proximal regions contain regulatory elements that are critical for their activity. Both proximal promoters contain CCAAT boxes and mutagenesis of these elements decreased significantly the activity of both promoters suggesting a coordinated regulation of the two genes by CCAAT box binding factors. Finally, we show that both genes are subjects to autoregulation in ESCs and in the case of RhoB, this autoregulation requires the GTPase activity of the Rho proteins. Understanding the mechanisms that control the transcription of Rho GTPases in ESCs may shed new light into the still unknown roles of these proteins in stem cell functions.
[Mh] Termos MeSH primário: Células-Tronco Embrionárias/fisiologia
Regulação da Expressão Gênica no Desenvolvimento/genética
Regiões Promotoras Genéticas/genética
Elementos Reguladores de Transcrição/genética
Proteína rhoA de Ligação ao GTP/genética
Proteína rhoB de Ligação ao GTP/genética
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Camundongos
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
EC 3.6.5.2 (rhoA GTP-Binding Protein); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170912
[Lr] Data última revisão:
170912
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170726
[St] Status:MEDLINE


  3 / 471 MEDLINE  
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[PMID]:28505515
[Au] Autor:Liu S; Huang L; Lin Z; Hu Y; Chen R; Wang L; Shan Y
[Ad] Endereço:Emergency Department of Navy General Hospital, Beijing, 100037, China.
[Ti] Título:RhoB induces the production of proinflammatory cytokines in TLR-triggered macrophages.
[So] Source:Mol Immunol;87:200-206, 2017 Jul.
[Is] ISSN:1872-9142
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Toll-like receptors (TLRs) are the primary sensors detecting conserved molecular patterns on microorganisms, thus acting as important components of innate immunity against invading pathogens. Many positive and negative regulators of TLR-triggered signaling have been identified. The Rho GTPase RhoB plays a key role in cell migration, division and polarity; however, the function and regulatory mechanisms of RhoB in TLR ligand-triggered innate immune responses remain to be investigated. Here, we report that the expression of RhoB is induced by TLR agonists (lipopolysaccharide (LPS), CpG, poly(I:C)) in macrophages. Knockdown of RhoB expression markedly decreased TLR ligand-induced activation of mitogen activated protein kinases and nuclear factor-κB (NF-κB), and the production of tumor necrosis factor α (TNFα), interleukin (IL)-6 and IL-1ß in macrophages stimulated with TLR ligands. Furthermore, we demonstrated that RhoB interacts with major histocompatibility complex class II (MHCII) α chain, but not ß chain, in endosomes of macrophages. Knockdown of MHCII expression greatly reduced the interaction of RhoB with Btk, and attenuated the induction of NF-κB and interferon ß activity by RhoB upon LPS stimulation. These findings suggest that RhoB is a positive physiological regulator of TLRs signaling via binding to MHCII in macrophages, and therefore RhoB may be a potential therapeutic target in inflammatory diseases.
[Mh] Termos MeSH primário: Citocinas/metabolismo
Inflamação/metabolismo
Macrófagos/metabolismo
Receptores Toll-Like/metabolismo
Proteína rhoB de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Linhagem Celular
Genes MHC Classe II/fisiologia
Células HEK293
Seres Humanos
Imunidade Inata/fisiologia
Interferon beta/metabolismo
Interleucina-6/metabolismo
Lipopolissacarídeos/farmacologia
Macrófagos/efeitos dos fármacos
Camundongos
NF-kappa B/metabolismo
Poli I-C/metabolismo
Células RAW 264.7
Transdução de Sinais/efeitos dos fármacos
Transdução de Sinais/fisiologia
Fator de Necrose Tumoral alfa/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Interleukin-6); 0 (Lipopolysaccharides); 0 (NF-kappa B); 0 (Toll-Like Receptors); 0 (Tumor Necrosis Factor-alpha); 77238-31-4 (Interferon-beta); EC 3.6.5.2 (rhoB GTP-Binding Protein); O84C90HH2L (Poly I-C)
[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:170516
[St] Status:MEDLINE


  4 / 471 MEDLINE  
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[PMID]:28395021
[Au] Autor:Duluc L; Ahmetaj-Shala B; Mitchell J; Abdul-Salam VB; Mahomed AS; Aldabbous L; Oliver E; Iannone L; Dubois OD; Storck EM; Tate EW; Zhao L; Wilkins MR; Wojciak-Stothard B
[Ad] Endereço:Department of Medicine, Hammersmith Campus, Imperial College London, Du Cane Road, W120NN London, UK.
[Ti] Título:Tipifarnib prevents development of hypoxia-induced pulmonary hypertension.
[So] Source:Cardiovasc Res;113(3):276-287, 2017 Mar 01.
[Is] ISSN:1755-3245
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Aims: RhoB plays a key role in the pathogenesis of hypoxia-induced pulmonary hypertension. Farnesylated RhoB promotes growth responses in cancer cells and we investigated whether inhibition of protein farnesylation will have a protective effect. Methods and results: The analysis of lung tissues from rodent models and pulmonary hypertensive patients showed increased levels of protein farnesylation. Oral farnesyltransferase inhibitor tipifarnib prevented development of hypoxia-induced pulmonary hypertension in mice. Tipifarnib reduced hypoxia-induced vascular cell proliferation, increased endothelium-dependent vasodilatation and reduced vasoconstriction of intrapulmonary arteries without affecting cell viability. Protective effects of tipifarnib were associated with inhibition of Ras and RhoB, actin depolymerization and increased eNOS expression in vitro and in vivo. Farnesylated-only RhoB (F-RhoB) increased proliferative responses in cultured pulmonary vascular cells, mimicking the effects of hypoxia, while both geranylgeranylated-only RhoB (GG-RhoB), and tipifarnib had an inhibitory effect. Label-free proteomics linked F-RhoB with cell survival, activation of cell cycle and mitochondrial biogenesis. Hypoxia increased and tipifarnib reduced the levels of F-RhoB-regulated proteins in the lung, reinforcing the importance of RhoB as a signalling mediator. Unlike simvastatin, tipifarnib did not increase the expression levels of Rho proteins. Conclusions: Our study demonstrates the importance of protein farnesylation in pulmonary vascular remodelling and provides a rationale for selective targeting of this pathway in pulmonary hypertension.
[Mh] Termos MeSH primário: Anti-Hipertensivos/farmacologia
Inibidores Enzimáticos/farmacologia
Farnesiltranstransferase/antagonistas & inibidores
Hipertensão Pulmonar/prevenção & controle
Hipóxia/tratamento farmacológico
Artéria Pulmonar/efeitos dos fármacos
Quinolonas/farmacologia
[Mh] Termos MeSH secundário: Animais
Proliferação Celular/efeitos dos fármacos
Células Cultivadas
Modelos Animais de Doenças
Células Endoteliais/efeitos dos fármacos
Células Endoteliais/enzimologia
Células Endoteliais/patologia
Farnesiltranstransferase/metabolismo
Seres Humanos
Hipertensão Pulmonar/enzimologia
Hipertensão Pulmonar/etiologia
Hipóxia/complicações
Hipóxia/enzimologia
Masculino
Camundongos Endogâmicos C57BL
Fenótipo
Prenilação de Proteína
Proteômica/métodos
Artéria Pulmonar/enzimologia
Artéria Pulmonar/patologia
Artéria Pulmonar/fisiopatologia
Fatores de Tempo
Transfecção
Vasoconstrição/efeitos dos fármacos
Vasodilatação/efeitos dos fármacos
Proteína rhoB de Ligação ao GTP/genética
Proteína rhoB de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antihypertensive Agents); 0 (Enzyme Inhibitors); 0 (Quinolones); EC 2.5.1.29 (Farnesyltranstransferase); EC 3.6.5.2 (rhoB GTP-Binding Protein); MAT637500A (tipifarnib)
[Em] Mês de entrada:1710
[Cu] Atualização por classe:171002
[Lr] Data última revisão:
171002
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170411
[St] Status:MEDLINE
[do] DOI:10.1093/cvr/cvw258


  5 / 471 MEDLINE  
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[PMID]:28323887
[Au] Autor:Diao F; Chen K; Wang Y; Li Y; Xu W; Lu J; Chen YX
[Ad] Endereço:Department of Pathophysiology, Second Military Medical University, Shanghai, China.
[Ti] Título:Involvement of small G protein RhoB in the regulation of proliferation, adhesion and migration by dexamethasone in osteoblastic cells.
[So] Source:PLoS One;12(3):e0174273, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Long-term exposure to therapeutic doses of glucocorticoids (GCs) results in bone remodeling, which frequently causes osteoporosis and fracture healing retardation because of the abnormality of osteoblastic proliferation and differentiation. The mechanisms of GCs' effect on osteoblasts are largely unknown. In this present study, we found that dexamethasone (Dex) could induce the expression of the small G protein, RhoB, in mRNA and protein levels in the osteoblast-derived osteosarcoma cell lines MG-63. The up-regulation of RhoB mRNA by Dex mainly occurs at posttranscriptional level by increasing its mRNA stability through PI-3K/Akt and p38 mitogen-activated protein kinase signaling pathways. Over-expression of RhoB in MG-63 cells magnified while down-regulation of RhoB level by RNA interference impaired Dex-induced growth inhibition but not differentiation. What's more, over-expression of RhoB mimicked the effect of Dex on cell adhesion and migration. And interfering RhoB expression partially suppressed Dex-induced pro-adhesion and anti-migration in MG-63 cells. In conclusion, these results indicate that RhoB plays an important role in the pathological effect of Dex on osteoblastic growth and migration, which is a part of the mechanisms of GCs' adverse effect on bone remodeling.
[Mh] Termos MeSH primário: Desenvolvimento Ósseo/efeitos dos fármacos
Dexametasona/farmacologia
Osteoblastos/metabolismo
Fosfatidilinositol 3-Quinases/metabolismo
Proteínas Proto-Oncogênicas c-akt/metabolismo
Estabilidade de RNA/efeitos dos fármacos
Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo
Proteína rhoB de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Remodelação Óssea/fisiologia
Osso e Ossos/efeitos dos fármacos
Adesão Celular/fisiologia
Diferenciação Celular/fisiologia
Linhagem Celular Tumoral
Movimento Celular/fisiologia
Proliferação Celular/fisiologia
Seres Humanos
Interferência de RNA
RNA Mensageiro/biossíntese
Proteína rhoB de Ligação ao GTP/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (RNA, Messenger); 7S5I7G3JQL (Dexamethasone); EC 2.7.1.- (Phosphatidylinositol 3-Kinases); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170322
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0174273


  6 / 471 MEDLINE  
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[PMID]:28212429
[Au] Autor:Arsic N; Ho-Pun-Cheung A; Evelyne C; Assenat E; Jarlier M; Anguille C; Colard M; Pezet M; Roux P; Gadea G
[Ad] Endereço:CNRS, Centre de Recherche en Biologie cellulaire de Montpellier, Montpellier, France.
[Ti] Título:The p53 isoform delta133p53ß regulates cancer cell apoptosis in a RhoB-dependent manner.
[So] Source:PLoS One;12(2):e0172125, 2017.
[Is] ISSN:1932-6203
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:The TP53 gene plays essential roles in cancer. Conventionally, wild type (WT) p53 is thought to prevent cancer development and metastasis formation, while mutant p53 has transforming abilities. However, clinical studies failed to establish p53 mutation status as an unequivocal predictive or prognostic factor of cancer progression. The recent discovery of p53 isoforms that can differentially regulate cell cycle arrest and apoptosis suggests that their expression, rather than p53 mutations, could be a more clinically relevant biomarker in patients with cancer. In this study, we show that the p53 isoform delta133p53ß is involved in regulating the apoptotic response in colorectal cancer cell lines. We first demonstrate delta133p53ß association with the small GTPase RhoB, a well-described anti-apoptotic protein. We then show that, by inhibiting RhoB activity, delta133p53ß protects cells from camptothecin-induced apoptosis. Moreover, we found that high delta133p53 mRNA expression levels are correlated with higher risk of recurrence in a series of patients with locally advanced rectal cancer (n = 36). Our findings describe how a WT TP53 isoform can act as an oncogene and add a new layer to the already complex p53 signaling network.
[Mh] Termos MeSH primário: Apoptose
Neoplasias Colorretais/metabolismo
Neoplasias Colorretais/patologia
Proteína Supressora de Tumor p53/metabolismo
Proteína rhoB de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Linhagem Celular Tumoral
Neoplasias Colorretais/diagnóstico
Neoplasias Colorretais/genética
Progressão da Doença
Regulação Neoplásica da Expressão Gênica
Seres Humanos
Prognóstico
Ligação Proteica
Isoformas de Proteínas/genética
Isoformas de Proteínas/metabolismo
RNA Mensageiro/genética
RNA Mensageiro/metabolismo
Proteína Supressora de Tumor p53/genética
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Protein Isoforms); 0 (RNA, Messenger); 0 (Tumor Suppressor Protein p53); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1708
[Cu] Atualização por classe:170818
[Lr] Data última revisão:
170818
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170218
[St] Status:MEDLINE
[do] DOI:10.1371/journal.pone.0172125


  7 / 471 MEDLINE  
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[PMID]:28131418
[Au] Autor:Sun M; Nie FQ; Zang C; Wang Y; Hou J; Wei C; Li W; He X; Lu KH
[Ad] Endereço:Department of Oncology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, China; Department of Bioinformatics and Computational Biology, UT MD Anderson Cancer Center, Houston, TX 77030, USA.
[Ti] Título:The Pseudogene DUXAP8 Promotes Non-small-cell Lung Cancer Cell Proliferation and Invasion by Epigenetically Silencing EGR1 and RHOB.
[So] Source:Mol Ther;25(3):739-751, 2017 Mar 01.
[Is] ISSN:1525-0024
[Cp] País de publicação:United States
[La] Idioma:eng
[Ab] Resumo:Recently, the non-protein-coding functional elements in the human genome have been identified as key regulators in postgenomic biology, and a large number of pseudogenes as well as long non-coding RNAs (lncRNAs) have been found to be transcribed in multiple human cancers. However, only a small proportion of these pseudogenes has been functionally characterized. In this study, we screened for pseudogenes associated with human non-small-cell lung cancer (NSCLC) by comparative analysis of several independent datasets from the GEO. We identified a transcribed pseudogene named DUXAP8 that is upregulated in tumor tissues. Patients with higher DUXAP8 expression exhibited shorter survival, suggesting DUXAP8 as a new candidate prognostic marker for NSCLC patients. Knockdown of DUXAP8 impairs cell growth, migration, and invasion, and induces apoptosis both in vitro and in vivo. Mechanistically, DUXAP8 represses the tumor suppressors EGR1 and RHOB by recruiting histone demethylase LSD1 and histone methyltransferase EZH2, thereby promoting cell proliferation, migration, and invasion. These findings indicate that the pseudogene DUXAP8 may act as an oncogene in NSCLC by silencing EGR1 and RHOB transcription by binding with EZH2 and LSD1, which may offer a novel therapeutic target for this disease.
[Mh] Termos MeSH primário: Carcinoma Pulmonar de Células não Pequenas/genética
Canal de Potássio ERG1/genética
Epigênese Genética
Inativação Gênica
Neoplasias Pulmonares/genética
Pseudogenes/genética
Proteína rhoB de Ligação ao GTP/genética
[Mh] Termos MeSH secundário: Apoptose/genética
Carcinoma Pulmonar de Células não Pequenas/mortalidade
Ciclo Celular/genética
Linhagem Celular Tumoral
Proliferação Celular
Transformação Celular Neoplásica/genética
Análise por Conglomerados
Canal de Potássio ERG1/metabolismo
Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo
Perfilação da Expressão Gênica
Regulação Neoplásica da Expressão Gênica
Técnicas de Silenciamento de Genes
Histona Desmetilases/metabolismo
Seres Humanos
Neoplasias Pulmonares/mortalidade
Prognóstico
Ligação Proteica
Proteína rhoB de Ligação ao GTP/metabolismo
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (ERG1 Potassium Channel); EC 1.14.11.- (Histone Demethylases); EC 1.5.- (KDM1A protein, human); EC 2.1.1.43 (EZH2 protein, human); EC 2.1.1.43 (Enhancer of Zeste Homolog 2 Protein); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1706
[Cu] Atualização por classe:170606
[Lr] Data última revisão:
170606
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:170130
[St] Status:MEDLINE


  8 / 471 MEDLINE  
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[PMID]:28003335
[Au] Autor:Calvayrac O; Mazières J; Figarol S; Marty-Detraves C; Raymond-Letron I; Bousquet E; Farella M; Clermont-Taranchon E; Milia J; Rouquette I; Guibert N; Lusque A; Cadranel J; Mathiot N; Savina A; Pradines A; Favre G
[Ad] Endereço:Inserm, Centre de Recherche en Cancérologie de Toulouse, CRCT UMR-1037, Toulouse, France.
[Ti] Título:The RAS-related GTPase RHOB confers resistance to EGFR-tyrosine kinase inhibitors in non-small-cell lung cancer via an AKT-dependent mechanism.
[So] Source:EMBO Mol Med;9(2):238-250, 2017 Feb.
[Is] ISSN:1757-4684
[Cp] País de publicação:England
[La] Idioma:eng
[Ab] Resumo:Although lung cancer patients harboring EGFR mutations benefit from treatment with EGFR-tyrosine kinase inhibitors (EGFR-TKI), most of them rapidly relapse. RHOB GTPase is a critical player in both lung carcinogenesis and the EGFR signaling pathway; therefore, we hypothesized that it could play a role in the response to EGFR-TKI In a series of samples from EGFR-mutated patients, we found that low RHOB expression correlated with a good response to EGFR-TKI treatment while a poor response correlated with high RHOB expression (15.3 versus 5.6 months of progression-free survival). Moreover, a better response to EGFR-TKI was associated with low RHOB levels in a panel of lung tumor cell lines and in a lung-specific tetracycline-inducible EGFR transgenic mouse model. High RHOB expression was also found to prevent erlotinib-induced AKT inhibition in vitro and in vivo Furthermore, a combination of the new-generation AKT inhibitor G594 with erlotinib induced tumor cell death in vitro and tumor regression in vivo in RHOB-positive cells. Our results support a role for RHOB/AKT signaling in the resistance to EGFR-TKI and propose RHOB as a potential predictor of patient response to EGFR-TKI treatment.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carcinoma Pulmonar de Células não Pequenas/fisiopatologia
Resistência a Medicamentos
Proteínas Proto-Oncogênicas c-akt/metabolismo
Receptor do Fator de Crescimento Epidérmico/genética
Proteína rhoB de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Inibidores Enzimáticos/farmacologia
Seres Humanos
Camundongos
Camundongos Transgênicos
Proteínas Tirosina Quinases/antagonistas & inibidores
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Enzyme Inhibitors); EC 2.7.10.1 (EGFR protein, human); EC 2.7.10.1 (Protein-Tyrosine Kinases); EC 2.7.10.1 (Receptor, Epidermal Growth Factor); EC 2.7.11.1 (Proto-Oncogene Proteins c-akt); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1709
[Cu] Atualização por classe:170926
[Lr] Data última revisão:
170926
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161223
[St] Status:MEDLINE
[do] DOI:10.15252/emmm.201606646


  9 / 471 MEDLINE  
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[PMID]:27812856
[Au] Autor:Ansari SS; Akgün N; Berger MR
[Ad] Endereço:Toxicology and Chemotherapy Unit, Deutsches Krebsforschungszentrum, Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.
[Ti] Título:Erufosine increases RhoB expression in oral squamous carcinoma cells independent of its tumor suppressive mode of action - a short report.
[So] Source:Cell Oncol (Dordr);40(1):89-96, 2017 Feb.
[Is] ISSN:2211-3436
[Cp] País de publicação:Netherlands
[La] Idioma:eng
[Ab] Resumo:PURPOSE: Recently, we found that erufosine (erucylphospho-N,N,N trimethylpropylammonium) can induce up-regulation of RhoB expression in oral squamous carcinoma (OSCC) cells, thereby hinting at a tumor suppressive role. Therefore, we aimed to evaluate the role of RhoB in the tumor suppressive mode of action of erufosine on OSCC cells. METHODS: Anti-proliferative effects of erufosine were determined in HN-5 and FaDu OSCC-derived cells using a MTT assay. RhoB up-regulation was detected using microarray and qRT-PCR-based expression assays at IC , IC and IC concentrations of erufosine. The results obtained were verified by Western blotting. In addition, siRNA-mediated RhoB knockdown was carried out and combined with erufosine treatment, after which cell cycle, colony formation and migration assays were performed to evaluate its combined effects. RESULTS: We found that after erufosine treatment of HN-5 and FaDu cells for 24, 48 and 72 h the IC values ranged from 43 to 37 µM and 27- to 15 µM, respectively. Microarray and qRT-PCR-based expression analyses revealed RhoB up-regulation up to 9-fold and 20-fold, respectively. Using Western blotting, an increase in RhoB protein expression was observed, as well as a decrease in pAkt (Ser and Thr ) expression and an increase in PARP cleavage. Combined siRNA-mediated RhoB knockdown and erufosine treatment resulted in slightly reduced RhoB and pAkt levels compared to erufosine treatment alone. Subsequent cell cycle analyses revealed an increased apoptotic induction, but a reduced G2 cell cycle arrest, of the combination. At the functional level, synergistic effects were observed using cell migration and colony formation assays. CONCLUSIONS: Our data show that erufosine can cause up-regulation of RhoB expression in OSCC cells. Combining erufosine treatment with siRNA-mediated RhoB knockdown did, however, not reveal a role of RhoB in its tumor suppressive mode of action.
[Mh] Termos MeSH primário: Antineoplásicos/farmacologia
Carcinoma de Células Escamosas/metabolismo
Neoplasias Bucais/metabolismo
Organofosfatos/farmacologia
Compostos de Amônio Quaternário/farmacologia
Proteína rhoB de Ligação ao GTP/biossíntese
[Mh] Termos MeSH secundário: Western Blotting
Carcinoma de Células Escamosas/patologia
Linhagem Celular Tumoral
Técnicas de Silenciamento de Genes
Seres Humanos
Neoplasias Bucais/patologia
Análise de Sequência com Séries de Oligonucleotídeos
Reação em Cadeia da Polimerase em Tempo Real
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Antineoplastic Agents); 0 (Organophosphates); 0 (Quaternary Ammonium Compounds); 0 (erucylphospho-N,N,N-trimethylpropylammonium); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1701
[Cu] Atualização por classe:171111
[Lr] Data última revisão:
171111
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:161105
[St] Status:MEDLINE
[do] DOI:10.1007/s13402-016-0302-8


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[PMID]:26388235
[Au] Autor:Huang G; Su J; Zhang M; Jin Y; Wang Y; Zhou P; Lu J
[Ad] Endereço:Department of Pathophysiology, Second Military Medical University, Shanghai 200433, People's Republic of China.
[Ti] Título:RhoB regulates the function of macrophages in the hypoxia-induced inflammatory response.
[So] Source:Cell Mol Immunol;14(3):265-275, 2017 Mar.
[Is] ISSN:2042-0226
[Cp] País de publicação:China
[La] Idioma:eng
[Ab] Resumo:Immune cells, particularly macrophages, play critical roles in the hypoxia-induced inflammatory response. The small GTPase RhoB is usually rapidly induced by a variety of stimuli and has been described as an important regulator of cytoskeletal organization and vesicle and membrane receptor trafficking. However, it is unknown whether RhoB is involved in the hypoxia-induced inflammatory response. Here, we investigated the effect of hypoxia on the expression of RhoB and the mechanism and significance of RhoB expression in macrophages. We found that hypoxia significantly upregulated the expression of RhoB in RAW264.7 cells, mouse peritoneal macrophages, and the spleen of rats. Hypoxia-induced expression of RhoB was significantly blocked by a specific inhibitor of hypoxia-inducible factor-1α (HIF-1α), c-Jun N-terminal kinase (JNK), or extracellular-signal regulated protein kinase (ERK), indicating that hypoxia-activated HIF-1α, JNK, and ERK are involved in the upregulation of RhoB by hypoxia. Knockdown of RhoB expression not only significantly suppressed basal production of interleukin-1 beta (IL-1ß), interleukin 6 (IL-6), and tumor necrosis factor alpha (TNF-α) in normoxia but also more markedly decreased the hypoxia-stimulated production of these cytokines. Furthermore, we showed that RhoB increased nuclear factor-kappa B (NF-κB) activity, and the inhibition of NF-κB transcriptional activity significantly decreased the RhoB-increased mRNA levels of IL-1ß, IL-6, and TNF-α. Finally, we demonstrated that RhoB enhanced cell adhesion and inhibited cell migration in normoxia and hypoxia. Taken together, these results suggest that RhoB plays an important role in the hypoxia-induced activation of macrophages and the inflammatory response.Cellular & Molecular Immunology advance online publication, 21 September 2015; doi:10.1038/cmi.2015.78.
[Mh] Termos MeSH primário: Inflamação/metabolismo
Inflamação/patologia
Macrófagos/metabolismo
Macrófagos/patologia
Proteína rhoB de Ligação ao GTP/metabolismo
[Mh] Termos MeSH secundário: Animais
Adesão Celular
Hipóxia Celular
Movimento Celular
Citocinas/metabolismo
Técnicas de Silenciamento de Genes
Inativação Gênica
Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo
Mediadores da Inflamação/metabolismo
Sistema de Sinalização das MAP Quinases
Masculino
Camundongos
Camundongos Endogâmicos BALB C
Modelos Biológicos
NF-kappa B/metabolismo
Células RAW 264.7
Ratos
Baço/patologia
Regulação para Cima
[Pt] Tipo de publicação:JOURNAL ARTICLE
[Nm] Nome de substância:
0 (Cytokines); 0 (Hypoxia-Inducible Factor 1, alpha Subunit); 0 (Inflammation Mediators); 0 (NF-kappa B); EC 3.6.5.2 (rhoB GTP-Binding Protein)
[Em] Mês de entrada:1707
[Cu] Atualização por classe:170914
[Lr] Data última revisão:
170914
[Sb] Subgrupo de revista:IM
[Da] Data de entrada para processamento:150922
[St] Status:MEDLINE
[do] DOI:10.1038/cmi.2015.78



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