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1.
Sci Data ; 11(1): 463, 2024 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-38714688

RESUMO

Adverse perinatal factors can interfere with the normal development of the brain, potentially resulting in long-term effects on the comprehensive development of children. Presently, the understanding of cognitive and neurodevelopmental processes under conditions of adverse perinatal factors is substantially limited. There is a critical need for an open resource that integrates various perinatal factors with the development of the brain and mental health to facilitate a deeper understanding of these developmental trajectories. In this Data Descriptor, we introduce a multicenter database containing information on perinatal factors that can potentially influence children's brain-mind development, namely, periCBD, that combines neuroimaging and behavioural phenotypes with perinatal factors at county/region/central district hospitals. PeriCBD was designed to establish a platform for the investigation of individual differences in brain-mind development associated with perinatal factors among children aged 3-10 years. Ultimately, our goal is to help understand how different adverse perinatal factors specifically impact cognitive development and neurodevelopment. Herein, we provide a systematic overview of the data acquisition/cleaning/quality control/sharing, processes of periCBD.


Assuntos
Encéfalo , Desenvolvimento Infantil , Criança , Pré-Escolar , Humanos , Encéfalo/crescimento & desenvolvimento , Encéfalo/diagnóstico por imagem , China , Cognição , Bases de Dados Factuais , Neuroimagem
2.
Front Psychiatry ; 14: 1116369, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36778631

RESUMO

Developmental coordination disorder (DCD) is a motor development disorder that affects an individual's growth and development, and may persist throughout life. It is not caused by intellectual or physical disability. Studies have suggested DCD often occurs in childhood, resulting in a series of abnormal manifestations that hinder children's normal development; cohort studies suggest a higher incidence in boys than in girls. Early diagnosis and appropriate interventions can help relieve symptoms. Unfortunately, the relevant research still needs to be further developed. In this paper, we first start from the definition of DCD, systematically investigate the relevant research papers in the past decades and summarize the current research hotspots and research trends in this field. After summarizing, it is found that this research field has attracted more researchers to join, the number of papers published has increased year by year and has become a hot spot in multidisciplinary research, such as education, psychology, sports rehabilitation, neurobiology, and neuroimaging. The continuous development of the correlation between perinatal factors and DCD, various omics studies, and neuroimaging methods also brings new perspectives and working targets to DCD research. DCD-related research will continue to deepen along the research direction of multivariate, multidimensional, and multimodal.

3.
Oncogene ; 42(1): 62-77, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36371565

RESUMO

Argonaute proteins, which consist of AGO1, AGO2, AGO3 and AGO4, are key players in microRNA-mediated gene silencing. So far, few non-microRNA related biological roles of AGO4 have been reported. Here, we first found that AGO4 had low expression in non-small cell lung cancer (NSCLC) patient tumor tissues and could suppress NSCLC cell proliferation and metastasis. Subsequent studies on the mechanism showed that AGO4 could interact with the tripartite motif-containing protein 21 (TRIM21) and the glucose-regulated protein 78 (GRP78). AGO4 promoted ubiquitination of GRP78 by stabilizing TRIM21, a new specific ubiquitin E3 ligase for promoting K48-linked polyubiquitination of GRP78 confirmed in this paper, which resulted in induced cell apoptosis and inhibited autophagy by activating mTOR signal pathway. Further studies showed that p53 had dominant effects on TRIM21-GRP78 axis by directly increasing the expression of TRIM21 in p53 wild-type cells and AGO4 may alternatively regulate TRIM21-GRP78 axis in p53-deficient cells. We also found that overexpression of AGO4 results in suppression of multiple p53-deficient cell growth both in vivo and vitro. Together, we showed for the first time that the AGO4-TRIM21-GRP78 axis, as a new regulatory pathway, may be a novel potential therapeutic target for p53-deficient tumor treatment.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , Humanos , Apoptose/genética , Chaperona BiP do Retículo Endoplasmático , Neoplasias Pulmonares/genética , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo , Ubiquitinação
4.
Toxicol Appl Pharmacol ; 451: 116167, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-35842139

RESUMO

The T-2 toxin is a highly toxic trichothecene mycotoxin that would cause serious toxicity in humans and animals. Recent studies suggest that the central nervous system (CNS) is susceptible to T-2 toxin, which can easily cross the blood-brain barrier, accumulate in brain tissues, and cause neurotoxicity. The growing evidence indicates that oxidative damage and mitochondrial dysfunction play a critical role in T-2 toxin-induced neurotoxicity, but the mechanisms are still poorly understood. Our present study showed that T-2 toxin decreased cell viability and increased lactate dehydrogenase leakage in human neuroblastoma SH-SY5Y cells in a concentration- and time-dependent manner. T-2 toxin elicited prominent oxidative stress and mitochondrial dysfunction, as evidenced by the promotion of cellular reactive oxygen species generation, disruption of the mitochondrial membrane potential, depletion of glutathione and reduction of the cellular ATP content. T-2 toxin impaired mitochondrial biogenesis, including decreased mitochondrial DNA copy number and affected the nuclear factor erythroid 2 related factor 2 (NRF2) / peroxisome proliferator-activated receptor γ coactivator 1 alpha (PGC-1α) pathway by upregulating NRF2 mRNA and protein expression while inhibiting the expression of PGC-1α, nuclear respiratory factor (NRF1) and mitochondrial transcription factor A (TFAM). NRF2 knockdown was found to significantly exacerbate T-2 toxin-induced cytotoxicity, oxidative stress, and mitochondrial dysfunction, as well as aggravate mitochondrial biogenesis impairment. NRF2 knockdown compromised T-2 toxin-induced upregulation of NRF2, but augmented the inhibition of PGC-1α, NRF1, and TFAM by T-2 toxin. Taken together, these findings suggest that T-2 toxin-induced oxidative stress and mitochondrial dysfunction in SH-SY5Y cells, at least in part by, NRF2/PGC-1α pathway-mediated mitochondrial biogenesis.


Assuntos
Neuroblastoma , Toxina T-2 , Animais , DNA Mitocondrial/metabolismo , Humanos , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Biogênese de Organelas , Estresse Oxidativo , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/genética , Coativador 1-alfa do Receptor gama Ativado por Proliferador de Peroxissomo/metabolismo , Toxina T-2/toxicidade
5.
Virulence ; 12(1): 1980-1996, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34338598

RESUMO

Complement receptor 3 (CD11b/CD18) is an important receptor that mediates adhesion, phagocytosis and chemotaxis in various immunocytes. The conidia of the medically-important pathogenic fungus, Aspergillus fumigatus can be internalized into alveolar epithelial cells to disseminate its infection in immunocompromised host; however, the role of CR3 in this process is poorly understood. In the present study, we investigated the potential role of CR3 on A. fumigatus internalization into type II alveolar epithelial cells and its effect on host intracellular PA content induced by A. fumigatus. We found that CR3 is expressed in alveolar epithelial cells and that human serum and bronchoalveolar lavage fluid (BALF) could improve A. fumigatus conidial internalization into A549 type II alveolar epithelial cell line and mouse primary alveolar epithelial cells, which were significantly inhibited by the complement C3 quencher and CD11b-blocking antibody. Serum-opsonization of swollen conidia, but not resting conidia led to the increase of cellular phosphatidic acid (PA) in A549 cells during infection. Moreover, both conidial internalization and induced PA production were interfered by CD11b-blocking antibody and dependent on FAK activity, but not Syk in alveolar epithelial cells. Overall, our results revealed that CR3 is a critical modulator of Aspergillus fumigatus internalization into alveolar epithelial cells.


Assuntos
Células Epiteliais Alveolares , Aspergillus fumigatus , Antígeno CD11b/imunologia , Quinase 1 de Adesão Focal/imunologia , Ácidos Fosfatídicos/química , Células A549 , Células Epiteliais Alveolares/imunologia , Células Epiteliais Alveolares/microbiologia , Animais , Aspergilose/imunologia , Antígenos CD18 , Humanos , Camundongos , Opsonização , Esporos Fúngicos
6.
Front Microbiol ; 10: 1345, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275272

RESUMO

Aspergillus fumigatus is able to internalize into lung epithelial cells to escape from immune attack for further dissemination. We previously reported that gliotoxin, a major mycotoxin of A. fumigatus, promotes this internalization; however, the mechanism remained unclear. Here, we report that gliotoxin is able to induce cofilin phosphorylation in A549 type II human pneumocytes. Either too high or too low a level of cofilin phosphorylation blocked the gliotoxin-induced actin cytoskeleton rearrangement and A. fumigatus internalization. LIM domain kinase 1 (LIMK1) and its upstream small GTPases (Cdc42 and RhoA, but not Rac1) predominantly mediated the gliotoxin-induced cofilin phosphorylation and A. fumigatus internalization. Simultaneously, gliotoxin significantly stimulated an increase in cAMP; however, adding an antagonist of PKA did not block gliotoxin-induced A. fumigatus internalization. In vivo, exogenous gliotoxin helped gliotoxin synthesis deficient strain gliPΔ invade into the lung tissue and the lung fungal burden increased markedly in immunosuppressed mice. In conclusion, these data revealed a novel role of gliotoxin in inducing cofilin phosphorylation mostly through the Cdc42/RhoA-LIMK1 signaling pathway to promote actin cytoskeleton rearrangement and internalization of A. fumigatus into type II human pneumocytes.

7.
Fungal Genet Biol ; 120: 30-41, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30205199

RESUMO

Aspergillus fumigatus is a major pathogen of invasive pulmonary aspergillosis. The small GTPase, Rho1, of A. fumigatus is reported to comprise a potential regulatory subunit of ß-1,3-glucan synthase and is indispensable for fungal viability; however, the role of AfRho1 on the growth, cell wall integrity, and pathogenesis of A. fumigatus is still poorly understood. We constructed A. fumigatus mutants with conditional- and overexpression of Rho1 and found that defects of AfRho1 expression led to the reduction of ß-1,3-glucan and glucosamine moieties on the cell wall, with down-regulated transcription of genes in the cell wall integrity signaling pathway and a decrease of calcofluor white (CFW)-stimulated mitogen-activated protein kinase (MpkA) phosphorylation and cytoplasmic leakage compared to those of the wild-type strain (WT). In addition, down-regulation of AfRho1 expression caused much higher sensitivity of A. fumigatus to H2O2 and alkaline pH compared to that of WT. Decrease of AfRho1 expression also attenuated the A. fumigatus pathogenicity in Galleria mellonella and inhibited conidial internalization into lung epithelial cells and inflammatory factor release. In contrast, overexpression of Rho1 did not alter A. fumigatus morphology, susceptibility to cell wall stresses, or pathogenicity relative to its parental strain. Taken together, our findings support AfRho1 as an essential regulator of the cell wall integrity, stress response, and pathogenesis of A. fumigatus.


Assuntos
Aspergillus fumigatus/enzimologia , Parede Celular/fisiologia , Proteínas Fúngicas/fisiologia , Proteínas rho de Ligação ao GTP/fisiologia , Células A549 , Animais , Aspergilose/microbiologia , Aspergillus fumigatus/patogenicidade , Aspergillus fumigatus/fisiologia , Humanos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mariposas/microbiologia , Estresse Fisiológico , Virulência/genética
8.
Artigo em Inglês | MEDLINE | ID: mdl-29507067

RESUMO

The use of azole fungicides in agriculture is believed to be one of the main reasons for the emergence of azole resistance in Aspergillus fumigatus Though widely used in agriculture, imidazole fungicides have not been linked to resistance in A. fumigatus This study showed that elevated MIC values of imidazole drugs were observed against A. fumigatus isolates with TR34/L98H/S297T/F495I mutation, but not among isolates with TR34/L98H mutation. Short-tandem-repeat (STR) typing analysis of 580 A. fumigatus isolates from 20 countries suggested that the majority of TR34/L98H/S297T/F495I strains from China were genetically different from the predominant major clade comprising most of the azole-resistant strains and the strains with the same mutation from the Netherlands and Denmark. Alignments of sterol 14α-demethylase sequences suggested that F495I in A. fumigatus was orthologous to F506I in Penicillium digitatum and F489L in Pyrenophora teres, which have been reported to be associated with imidazole resistance. In vitro antifungal susceptibility testing of different recombinants with cyp51A mutations further confirmed the association of the F495I mutation with imidazole resistance. In conclusion, this study suggested that environmental use of imidazole fungicides might confer selection pressure for the emergence of azole resistance in A. fumigatus.


Assuntos
Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Sistema Enzimático do Citocromo P-450/genética , Farmacorresistência Fúngica/genética , Proteínas Fúngicas/genética , Imidazóis/farmacologia , Esterol 14-Desmetilase/genética , Agricultura/métodos , Sequência de Aminoácidos , Aspergilose/tratamento farmacológico , Aspergillus fumigatus/isolamento & purificação , Humanos , Testes de Sensibilidade Microbiana , Seleção Genética/genética , Alinhamento de Sequência
9.
Artigo em Inglês | MEDLINE | ID: mdl-29483117

RESUMO

Through some specific amino acid residues, cofilin, a ubiquitous actin depolymerization factor, can significantly affect mitochondrial function related to drug resistance and apoptosis in Saccharomyces cerevisiae; however, this modulation in a major fungal pathogen, Aspergillus fumigatus, was still unclear. Hereby, it was found, first, that mutations on several charged residues in cofilin to alanine, D19A-R21A, E48A, and K36A, increased the formation of reactive oxygen species and induced apoptosis along with typical hallmarks, including mitochondrial membrane potential depolarization, cytochrome c release, upregulation of metacaspases, and DNA cleavage, in A. fumigatus Two of these mutations (D19A-R21A and K36A) increased acetyl coenzyme A and ATP concentrations by triggering fatty acid ß-oxidation. The upregulated acetyl coenzyme A affected the ergosterol biosynthetic pathway, leading to overexpression of cyp51A and -B, while excess ATP fueled ATP-binding cassette transporters. Besides, both of these mutations reduced the susceptibility of A. fumigatus to azole drugs and enhanced the virulence of A. fumigatus in a Galleria mellonella infection model. Taken together, novel and key charged residues in cofilin were identified to be essential modules regulating the mitochondrial function involved in azole susceptibility, apoptosis, and virulence of A. fumigatus.


Assuntos
Fatores de Despolimerização de Actina/genética , Antifúngicos/farmacologia , Apoptose/genética , Aspergillus fumigatus/efeitos dos fármacos , Aspergillus fumigatus/genética , Azóis/farmacologia , Farmacorresistência Fúngica/genética , Mitocôndrias/metabolismo , Transportadores de Cassetes de Ligação de ATP/metabolismo , Acetilcoenzima A/biossíntese , Aspergillus fumigatus/patogenicidade , Sistema Enzimático do Citocromo P-450/biossíntese , Ergosterol/biossíntese , Proteínas Fúngicas/biossíntese , Humanos , Virulência/genética
10.
Sci Rep ; 7(1): 15933, 2017 Nov 21.
Artigo em Inglês | MEDLINE | ID: mdl-29162852

RESUMO

Although belonging to one of the most common type of nosocomial infection, there was currently no simple prediction model for lower respiratory tract infections (LRTIs). This study aims to develop a risk index based system for predicting nosocomial LRTIs based on data from a large point-prevalence survey. Among the 49328 patients included, the prevalence of nosocomial LRTIs was 1.70% (95% confidence interval [CI], 1.64% to 1.76%). The areas under the receiver operating characteristic (ROC) curve for logistic regression and fisher discriminant analysis were 0.907 (95% CI, 0.897 to 0.917) and 0.902 (95% CI, 0.892 to 0.912), respectively. The constructed risk index based system also displayed excellent discrimination (area under the ROC curve: 0.905 [95% CI, 0.895 to 0.915]) to identify LRTI in internal validation. Six risk levels were generated according to the risk score distribution of study population, ranging from 0 to 5, the corresponding prevalence of nosocomial LRTIs were 0.00%, 0.39%, 3.86%, 12.38%, 28.79% and 44.83%, respectively. The sensitivity and specificity of prediction were 0.87 and 0.79, respectively, when the best cut-off point of risk score was set to 14. Our study suggested that this newly constructed risk index based system might be applied to boost more rational infection control programs in clinical settings.


Assuntos
Infecção Hospitalar/diagnóstico , Infecção Hospitalar/epidemiologia , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia , Análise Discriminante , Humanos , Modelos Logísticos , Prevalência , Curva ROC , Fatores de Risco
11.
Sci Rep ; 7(1): 7153, 2017 08 02.
Artigo em Inglês | MEDLINE | ID: mdl-28769054

RESUMO

GADD45A (growth arrest and DNA damage inducible alpha), a stress response gene induced by genotoxic and nongenotoxic stresses, is implicated in various key processes, including the control of cell cycle checkpoints and DNA repair. The expression of GADD45A is directly regulated by numerous transcription factors, with p53 being the most representative. Moreover, post-transcriptional regulation also plays a role in GADD45A expression. However, little is known about the regulatory effects of microRNAs (miRNAs) on GADD45A expression. As a potential tumour suppressor, miR-138 has pleiotropic biological functions in various cancers. We have previously reported p53-mediated activation of miR-138 in human non-small-cell lung cancer (NSCLC) cells. In this study, we found that miR-138 specifically targeted AGO2, which affects the stability and maturation of miR-130b. Decreased expression of miR-130b promoted the expression of GADD45A and resulted in the G2/M phase arrest and proliferation inhibition in human NSCLC cells. Our results suggested that p53 could alternatively upregulate GADD45A in human NSCLC cells through a post-transcriptional pathway in which miR-138 is involved.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Proteínas de Ciclo Celular/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/metabolismo , MicroRNAs/genética , Proteínas Nucleares/genética , Proteína Supressora de Tumor p53/metabolismo , Regiões 3' não Traduzidas , Proteínas Argonautas/genética , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Biológicos , Interferência de RNA , Processamento Pós-Transcricional do RNA , Transdução de Sinais
12.
Future Microbiol ; 12: 853-866, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28699775

RESUMO

AIM: To assess the effectiveness of antibiotic therapy against five indicator bacteria in a Chinese hospital using an index-based approach. METHODS: The study population comprises 1031 patients who had one clinically significant bacterial isolate in 2008, 2010 and 2013. Drug resistance index (DRI) based on pathogens was calculated. RESULTS: The adaptive DRIs for Klebsiella pneumoniae, Pseudomonas aeruginosa, Staphylococcus aureus decreased, while both adaptive and fixed DRIs for Acinetobacter spp. increased from 2008 to 2013. The adaptive DRIs for Escherichia coli increased from 2008 to 2013, while the fixed DRIs exhibited a decreasing trend. CONCLUSION: DRI could be used to demonstrate the changes of antimicrobial resistance and prescribing over time as a result of evolutionary processes and governmental regulatory interference.


Assuntos
Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Hospitais , Acinetobacter/efeitos dos fármacos , Antibacterianos/administração & dosagem , Antibacterianos/uso terapêutico , Bactérias/patogenicidade , Pequim , Infecção Hospitalar/tratamento farmacológico , Farmacorresistência Bacteriana/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Humanos , Controle de Infecções , Klebsiella pneumoniae/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Medicamentos sob Prescrição , Pseudomonas aeruginosa/efeitos dos fármacos , Staphylococcus aureus/efeitos dos fármacos
13.
Sci Rep ; 6: 26187, 2016 05 17.
Artigo em Inglês | MEDLINE | ID: mdl-27183959

RESUMO

In recent years, p53 was identified to regulate the expression of many miRNAs and was also regulated by miRNAs. In this paper, we found that miR-138 showed a pronounced increase after p53 activation in human non-small cell lung cancer (NSCLC) cells, which is mediated by p53 binding sites in the promoter region of its host gene, but this did not happen with rat and mouse cells. More interestingly, we found that p53 could be also regulated by miR-138 in mouse and rat cells, but not in the human NSCLC cells. Our results suggest the existence of species-specific differences of the regulations of miRNA against its targets and the regulations of miRNA itself by other proteins.


Assuntos
Regulação da Expressão Gênica , MicroRNAs/metabolismo , Proteína Supressora de Tumor p53/metabolismo , Animais , Linhagem Celular , Humanos , Camundongos , Ratos
14.
Int J Biol Sci ; 11(8): 961-9, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26157350

RESUMO

Vasorin (VASN) is a type I transmembrane protein that plays important roles in tumor development and vasculogenesis. In this paper, we showed that VASN could be a key mediator of communication between tumor cells and endothelial cells. We confirmed for the first time that HepG2-derived VASN can be transferred to human umbilical vein endothelial cells (HUVECs) via receptor mediated endocytosis of exosomes, at least in part through HSPGs. The HepG2-derived VASN containing exosomes promote migration of recipient HUVECs cells. Our results identify a novel pathway by which a functional protein expressed in tumor cells affects the biological fate of endothelial cells via exosomes.


Assuntos
Carcinoma Hepatocelular/metabolismo , Proteínas de Transporte/metabolismo , Movimento Celular/fisiologia , Exossomos/metabolismo , Neoplasias Hepáticas/metabolismo , Proteínas de Membrana/metabolismo , Carcinoma Hepatocelular/patologia , Proteínas de Transporte/fisiologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Neoplasias Hepáticas/patologia , Proteínas de Membrana/fisiologia , Transporte Proteico
15.
Biomaterials ; 63: 168-76, 2015 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-26107993

RESUMO

In this study, we further investigated a previously developed aptamer targeting ROS 17/2.8 (rat osteosarcoma) cells. We found that this C6-8 aptamer specifically binds to heterogeneous nuclear ribonucleoprotein (hnRNP) A2/B1 and that it specifically labeled multiple tumor-cell lines as effectively as hnRNP A2/B1 monoclonal antibodies. When conjugated with fluorescent carbon nanodots (CDots) it could freely enter multiple living tumor cell lines (HepG2, MCF-7, H1299, and HeLa), whose growth it inhibited by targeting hnRNP A2/B1. Similar inhibitory effects were observed when the GFP-HepG2 hepatocarcinoma cells treated with C6-8-conjugated CDots were implanted in nude mice. Our work provides a new aptamer for targeting/labeling multiple tumor cell types, and its nanoparticle conjugates bring further advantages that increase its potential for use in cancer diagnosis and therapy.


Assuntos
Aptâmeros de Nucleotídeos/metabolismo , Aptâmeros de Nucleotídeos/farmacologia , Ribonucleoproteínas Nucleares Heterogêneas Grupo A-B/metabolismo , Nanoconjugados/química , Neoplasias/tratamento farmacológico , Animais , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/farmacocinética , Sequência de Bases , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sistemas de Liberação de Medicamentos , Humanos , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias/metabolismo , Neoplasias/patologia , Ratos
16.
Oncotarget ; 6(12): 10045-59, 2015 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-25826090

RESUMO

UNLABELLED: We report a new biomarker of hepatocarcinoma, vasorin (VASN), screened by a subtractive EMSA-SELEX strategy from AFP negative serum of hepatocellular carcinoma (HCC) patients with extrahepatic metastases. VASN was verified to be highly expressed in sera of 100 cases of HCC patients compared with 97 cases of normal persons and 129 cases of hepatitis patients. Further validation by Q-PCR,IFA and Western blot showed higher expression of VASN at mRNA and protein levels in HCC cell lines and HCC tissues than in normal controls. RNA interference and forced overexpression assays verified that VASN promotes cell proliferation and migration and inhibits apoptosis. Down-regulation of microRNA miR145 and miR146a is an important mechanism leading to high expression of VASN. CONCLUSION: As a membrane protein and/or as free protein, VASN may be an effective target for biological treatment of liver cancer and is a potential biomarker for HCC diagnosis. Small molecular nucleotides targeting VASN are promising biological therapies to HCC.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Hepatocelular/sangue , Proteínas de Transporte/sangue , Neoplasias Hepáticas/sangue , Proteínas de Membrana/sangue , Biomarcadores Tumorais/genética , Western Blotting , Proteínas de Transporte/genética , Ensaio de Desvio de Mobilidade Eletroforética/métodos , Humanos , Proteínas de Membrana/genética , Técnica de Seleção de Aptâmeros/métodos
17.
Life Sci ; 122: 26-36, 2015 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-25510861

RESUMO

AIMS: The aim of the study was to explore the effect of miR-200b on the development of human peripheral blood monocyte-deriveddendritic-cell (DC) and its mechanisms. MAIN METHODS: Expression levels of miR-200b and its predicted targets were measured by real time-PCR. Protein expression of WASF3 was determined by Western blot and immunohistochemistry. Human peripheral blood mononuclear cells (PBMCs) were isolated by Ficoll-Hypaque density gradient centrifugation from the buffy coat fraction of anticoagulated blood. Monocytes were purified from PBMCs using anti-CD14 microbeads. The immunophenotypes of DCs were tested by flow cytometry. KEY FINDINGS: A strong reduction in miR-200b expression was associated with human peripheral blood monocyte-derivedDC differentiation. The overexpression of miR-200b significantly reduced the numbers of protruding veils in mature DCs (mDCs) that are critical for promoting antigen-specificT-cell activation. Further experiments showed that miR-200b could regulate the function of DCs by targeting WASF3, a protein involved in cell movement and invasion. SIGNIFICANCE: Our results define an important function of miR-200b in the negative regulation of DC development and provide a potential form of miRNA-mediated cell therapy for diseases that range from auto-immunity to graft-versus-host disease.


Assuntos
Proliferação de Células , Células Dendríticas/citologia , Regulação da Expressão Gênica , Leucócitos Mononucleares/metabolismo , MicroRNAs/fisiologia , Monócitos/citologia , Família de Proteínas da Síndrome de Wiskott-Aldrich/metabolismo , Western Blotting , Movimento Celular , Células Cultivadas , Imunofluorescência , Humanos , Técnicas Imunoenzimáticas , Leucócitos Mononucleares/citologia , RNA Mensageiro/genética , RNA Interferente Pequeno/genética , Reação em Cadeia da Polimerase em Tempo Real , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Família de Proteínas da Síndrome de Wiskott-Aldrich/antagonistas & inibidores , Família de Proteínas da Síndrome de Wiskott-Aldrich/genética
18.
FEBS Lett ; 588(12): 2063-9, 2014 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-24813629

RESUMO

As a cleavage enzyme of precursor TNF-α, the high expression level of ADAM17 in endothelial cells is an important factor in atherosclerosis. In this study, we demonstrate that ADAM17 is the target of miR-152. We found that miR-152 could reduce TNF precursor cleavage and inhibit cell proliferation and migration by targeting ADAM17 in human umbilical vein endothelial cells (HUVECs). Furthermore, the expression pattern of miR-152 and corresponding target ADAM17 was opposite in HUVECs under hypoxic conditions. The levels of circulating miR-152 in AS patient sera were lower than those detected in the sera of normal individuals. Our results indicate that miR-152 may be involved in the development of human atherosclerosis and could be used as diagnostic biomarker or therapeutic target in atherosclerosis.


Assuntos
Proteínas ADAM/genética , Movimento Celular/genética , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , MicroRNAs/genética , Proteína ADAM17 , Animais , Aterosclerose/sangue , Aterosclerose/genética , Sequência de Bases , Proliferação de Células , Humanos , MicroRNAs/sangue
19.
Nucleic Acids Res ; 42(1): 458-74, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24057215

RESUMO

MicroRNAs (miRNAs) are a class of non-coding small RNAs that consist of ≈ 22 nt and are involved in several biological processes by regulating target gene expression. MiR-138 has many biological functions and is often downregulated in cancers. Our results showed that overexpression of miR-138 downregulated target RMND5A (required for meiotic nuclear division 5 homolog A) and reduced Exportin-5 stability, which results in decreased levels of pre-miRNA nuclear export in HeLa cells. We also found that miR-138 could significantly inhibit HeLa cell migration by targeting RMND5A. Our study therefore identifies miR-138-RMND5A-Exportin-5 as a previously unknown miRNA processing regulatory pathway in HeLa cells.


Assuntos
Proteínas de Transporte/genética , Regulação para Baixo , Carioferinas/metabolismo , MicroRNAs/metabolismo , Processamento Pós-Transcricional do RNA , Transporte Ativo do Núcleo Celular , Proteínas de Transporte/metabolismo , Movimento Celular , Núcleo Celular/metabolismo , Células HeLa , Humanos , Estabilidade Proteica , Precursores de RNA/metabolismo
20.
Nucleic Acid Ther ; 23(1): 29-34, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23205572

RESUMO

MicroRNAs (miRNAs) play important roles in tumorigenesis and metastasis. In this study, we investigated miR-200b expression in endometrial adenocarcinomas and normal adjacent tissues and found that miR-200b is more highly expressed in cancer tissues than in normal adjacent tissues. A novel target of miR-200b, tissue inhibitor of metalloproteinase 2 (TIMP2), was predicted using a bioinformatics approach and was confirmed in human endometrial cancer cell line HEC-1A cells by luciferase assay, quantitative real-time polymerase chain reaction, western blotting, and enzyme-linked immunosorbent assay. We found that miR-200b repressed TIMP2 expression at both the messenger RNA and protein levels, although a family member, miR-200a, had no such effect. Using reverse gelatin zymography, we showed that miR-200b enhances matrix metallopeptidase 2 (MMP2) activity by downregulating TIMP2 expression in HEC-1A cells. These data suggest that miR-200b may play an important role in the metastasis of endometrial adenocarcinomas.


Assuntos
Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Neoplasias do Endométrio/genética , Neoplasias do Endométrio/metabolismo , Metaloproteinase 2 da Matriz/genética , Metaloproteinase 2 da Matriz/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Inibidor Tecidual de Metaloproteinase-2/genética , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Regiões 3' não Traduzidas , Sequência de Bases , Linhagem Celular Tumoral , Regulação para Baixo , Feminino , Humanos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , RNA Neoplásico/genética , RNA Neoplásico/metabolismo
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