RESUMO
Comprehensive multi-omics data analyses have become an important means for understanding cancer incidence and progression largely driven by the availability of high-throughput sequencing technologies for genomes, proteomes, and transcriptomes. However, how tumor cells from the site of origin of the cancer begin to grow in other sites of the body is very poorly understood. In order to examine potential connections between different cancers and to gain an insight into the metastatic process, we conducted a multi-omics data analysis using data deposited in The Cancer Genome Atlas database. By combining somatic mutation data along with DNA methylation level and gene expression level data, we applied a Bayesian network analysis to detect the potential association among four distinct cancer types namely, Head and neck squamous cell carcinoma (Hnsc), Lung adenocarcinoma (Luad), Lung squamous cell carcinoma (Lusc), and Skin cutaneous melanoma (Skcm). Further validation based on the 'identification of somatic signatures' and the 'association rules analysis' confirmed these associations. Previous investigations have suggested that common risk factors and molecular abnormalities in cell-cycle regulation and signal transduction predominate among these cancers. This evidence indicates that our study provides a rational analysis and hopefully will help shed light on the links between different cancers and metastasis as a whole.
Assuntos
Metástase Neoplásica/genética , Teorema de Bayes , Análise Mutacional de DNA , Regulação Neoplásica da Expressão Gênica , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Modelos Genéticos , MutaçãoRESUMO
Chronic obstructive pulmonary disease (COPD) is an important respiratory disease with high mortality. Although smoking is the major environmental risk factor for the development of COPD, only 10% of heavy smokers develop symptomatic disease, suggesting association between genetic susceptibilities and environmental influences. In recent years, as one of the most widely studied genes including tests for associations between a genetic variant and COPD, epoxide hydrolase 1 (EPHX1) was found to be involved in the metabolism of tobacco smoke, an important risk factor of COPD. However, genetic associations with COPD identified in studies on EPHX1 are controversial. To address this issue, except for performing the meta-analysis, which specially added our current study on two polymorphisms (T337C and A416G) of EPHX1, we performed combined data mining based on functional prediction algorithms of nonsynonymous single-nucleotide polymorphisms and gene-based variable threshold testing. Genetic variations in EPHX1 did not affect COPD in Caucasian and Eastern Asian population, which is supported by recent evidence. We found no association between EPHX1 and COPD; however, a minor effect of EPHX1 on COPD risk was not completely excluded; further replication studies with large samples are needed to confirm our findings.
Assuntos
Epóxido Hidrolases/genética , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Idoso , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido IncorretoRESUMO
The long non-coding RNA MALAT-1 plays an important role in cancer prognosis. The present research aimed to elucidate its precise predictive value in various human carcinomas. A quantitative meta-analysis was performed by searching PubMed, Embase, Web of Science, and Cochrane Library (most recently, January 2015) databases, and extracting data from studies that investigated the association between MALAT-1 expression and survival outcomes in patients of various cancers. Pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated as a measure of generalized effect. This meta-analysis included 1317 cases from 12 datasets. Our investigation revealed that poor overall survival (OS; HR = 2.14, 95% CI = 1.74-2.64) and shortened disease-free, recurrence-free, disease-specific, or progression-free survival (HR = 2.13, 95% CI = 1.22-3.72) can be predicted by high MALAT-1 expression for various cancers. Moreover, elevated MALAT-1 levels significantly correlated with decreased OS in a renal cell carcinoma (RCC) subgroup (HR = 3.43, 95% CI = 1.80-6.53). These results imply that MALAT-1 can be used to predict unfavorable prognoses for several cancers, particularly RCC.
Assuntos
Carcinoma/genética , Regulação Neoplásica da Expressão Gênica , RNA Longo não Codificante/genética , Adulto , Idoso , Biomarcadores Tumorais , Carcinoma/diagnóstico , Carcinoma/terapia , Intervalo Livre de Doença , Humanos , Pessoa de Meia-IdadeRESUMO
Lipid-associated membrane proteins (LAMPs) are important in the pathogenicity of the Mycoplasma genus of bacteria. We investigated whether Mycoplasma hyopneumoniae LAMPs have pathogenic potential by inducing apoptosis in a St. Jude porcine lung epithelial cell line (SJPL). LAMPs from a pathogenic strain of M. hyopneumoniae (strain 232) were used in the research. Our investigation made use of diamidino-phenylindole (DAPI) and acridine orange/ethidium bromide (AO/EB) staining, terminal dexynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) analysis, and Annexin-V-propidium iodide staining. After LAMP treatment for 24 h, typical changes were induced, chromosomes were concentrated, apoptotic bodies were observed, the 3'-OH groups of cleaved genomes were exposed, and the percentage of apoptotic cells reached 36.5 ± 11.66%. Caspase 3 and caspase 8 were activated and cytochrome c (cyt c) was released from the mitochondria into the cytoplasm; poly ADP ribose polymerase (PARP) was digested into two fragments; p38 mitogen-activated protein kinase (MAPK) was phosphorylated; and the expression of pro-apoptosis protein Bax increased while the anti-apoptosis protein Bcl-2 decreased. LAMPs also stimulated SJPL cells to produce nitric oxide (NO) and superoxide. This study demonstrated that LAMPs from M. hyopneumoniae can induce apoptosis in SJPL cells through the activation of caspase 3, caspase 8, cyt c, Bax, and p38 MAPK, thereby contributing to our understanding of the pathogenesis of M. hyopneumoniae, which should improve the treatment of M. hyopneumoniae infections.
Assuntos
Apoptose , Proteínas de Bactérias/farmacologia , Caspase 3/metabolismo , Células Epiteliais/citologia , Pulmão/citologia , Sistema de Sinalização das MAP Quinases , Mycoplasma hyopneumoniae/metabolismo , Animais , Caspase 8/metabolismo , Morte Celular/efeitos dos fármacos , Linhagem Celular , Núcleo Celular/efeitos dos fármacos , Núcleo Celular/metabolismo , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/metabolismo , Ativação Enzimática/efeitos dos fármacos , Células Epiteliais/efeitos dos fármacos , Células Epiteliais/enzimologia , Marcação In Situ das Extremidades Cortadas , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Modelos Biológicos , Óxido Nítrico/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Superóxidos/metabolismo , Sus scrofa , Proteína X Associada a bcl-2/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismoRESUMO
PURPOSE: The present study aimed at investigating the role and potential mechanism of geranylgeranyltransferase I (GGTase-I) on glioma cell migration and invasion. METHODS: Wound-healing assay and transwell assay were performed to study whether GGTase-I and Ras-like GTPase B (RalB) have effect on glioma cell migration and invasion. RESULTS: We found that knockdown of GGTase-I or RalB both significantly decreased the migratory and invasive abilities of glioma cells. GGTase-I down-regulation suppressed RalB membrane association. Moreover, down-regulation of RalB partially abolished the effect of GGTß over-expression-induced glioma cell migration and invasion increase. CONCLUSIONS: These findings suggest that RalB might be one of the targets for facilitating the invasive phenotype of malignant gliomas induced by GGTase-I.
Assuntos
Alquil e Aril Transferases/metabolismo , Glioma/patologia , Invasividade Neoplásica/patologia , Proteínas ral de Ligação ao GTP/metabolismo , Western Blotting , Linhagem Celular Tumoral , Movimento Celular/fisiologia , Humanos , RNA Interferente Pequeno , TransfecçãoRESUMO
Evidence has shown that miR-146a is involved in carcinogenesis and a common G/C variant (rs2910164) in the pre-miR-146a gene has been found to be associated with various cancers. We investigated the potential prognostic role of miR-146a polymorphism in prostate cancer after radical prostatectomy. Seventy-two southern Chinese with prostate cancer undergoing radical prostatectomy were included in this study. miR-146a polymorphism was analyzed by PCR-RFLP. Its prognostic role in biochemical recurrence was assessed using Kaplan-Meier analysis and Cox regression model. We did not find a significant association between miR-146a polymorphism and prostrate-specific antigen failure in the Chinese population [HR (95%CI): 0.83 (0.30-2.32) for CC vs GG/GC]. However, high Gleason score (over 8) was associated with increased biochemical recurrence and poorer PSA-free survival. This study was limited by the length of follow-up. Future studies with longer follow-up would allow evaluation of more direct metrics, such as disease-specific survival, metastasis-free survival, and overall survival.
Assuntos
MicroRNAs/genética , Polimorfismo Genético , Prostatectomia/estatística & dados numéricos , Neoplasias da Próstata/diagnóstico , Idoso , China , Humanos , Masculino , Prognóstico , Antígeno Prostático Específico/metabolismo , Neoplasias da Próstata/genética , Neoplasias da Próstata/cirurgia , Recidiva , Fatores de RiscoRESUMO
The insulin-like growth factor I (IGF-1) gene plays important roles in the growth and body composition of animals. Serum IGF1 concentration has been associated with growth traits in many livestock species. We found a polymorphism of cattle IGF1-TasI locus and analyzed the distribution of alleles in three cattle breeds, including Qinchuan, Nanyang, and Chinese Holstein. PCR-RFLP analysis showed that allele A was the dominant allele. The frequencies of allele A varied from 0.84 to 0.97. Distributions of genotypic and allelic frequencies were significantly different among breeds. Polymorphism of the IGF1 gene was significantly affecting hucklebone width at 6 months in the Nanyang breed and protein and fat yield of the third lactation in Chinese Holstein cattle. Individuals with allele C had a significantly higher performance in production traits.
Assuntos
Regiões 5' não Traduzidas/genética , Bovinos/genética , Fator de Crescimento Insulin-Like I/genética , Polimorfismo de Nucleotídeo Único , Alelos , Animais , Animais Recém-Nascidos , Composição Corporal/genética , Pesos e Medidas Corporais , Bovinos/classificação , Bovinos/crescimento & desenvolvimento , China , Feminino , Frequência do Gene , Estudos de Associação Genética/métodos , Genótipo , Masculino , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de Restrição , Especificidade da Espécie , Fatores de TempoRESUMO
The Jiangquhai porcine lean strain (JQHPL) is a new pork meat-type strain that has been developed in recent years from the parent lines Duroc, Fengjing, and Jiangquhai pigs (DurocxFengjing pigxJiangquhai pig). Enzootic pneumonia (EP) in pigs induced by Mycoplasma hyopneumoniae (M. hyopneumoniae) is a chronic respiratory disease of pigs, generating high economic losses in the swine industry. Here, we investigated the degree of resistance to M. hyopneumoniae for the Jiangquhai porcine lean strain and the Duroc x Landrace x Yorkshire (DLY) pigs, which are Western commercial pigs that have been introduced in China. A total of 209 DLY piglets and 221 JQHPL piglets from 19 Landrace x Yorkshire and 22 JQHPL M. hyopneumoniae positive gestating sows with different expected dates of confinement were selected and raised in the same M. hyopneumoniae positive farrowing barn. When the oldest suckling piglets were 37 days old, nasal swabs were collected from all the piglets (ranging from 4 to 37 days old) to detect the M. hyopneumoniae pathogen using n-PCR and M. hyopneumoniae specific SIgA using ELISA. Positive M. hyopneumoniae infection rates in both the strains increased with age; however, positive rates for JQHPL were lower compared to DLY at 14 to 35 days old. The level of the specific SIgA rose rapidly in JQHPL respiratory tracts, particularly in piglets 21 to 35 days in age compared to DLY piglets of the same age; however, the level of the specific SIgA in DLY also marginally increased. In conclusion, JQHPL pigs exhibits higher resistance to M. hyopneumoniae compared to DLY. It is possible that this characteristic is caused by the faster and stronger mucosal immunity phenotype of the JQHPL strain.
Assuntos
Anticorpos Antibacterianos/biossíntese , Imunidade nas Mucosas , Imunoglobulina A/biossíntese , Carne , Mycoplasma hyopneumoniae/imunologia , Pneumonia Suína Micoplasmática/imunologia , Fatores Etários , Animais , Animais Lactentes , Cruzamento , Feminino , Mucosa Nasal/imunologia , Mucosa Nasal/microbiologia , Pneumonia Suína Micoplasmática/microbiologia , Gravidez , SuínosRESUMO
Our objective was to investigate the distributions of six single nucleotide polymorphisms (SNPs) MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA I75V, IL4 C-590T, and IL13 C1923T in Mauritian Indian and Chinese Han children with asthma. This case-control association study enrolled 382 unrelated Mauritian Indian children, 193 with asthma and 189 healthy controls, and 384 unrelated Chinese Han children, 192 with asthma and 192 healthy controls. The SNP loci were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism for the Chinese Han samples and TaqMan real-time quantitative PCR for the Mauritian Indian samples. In the Mauritian Indian children, there was a significant difference in the distribution of IL13 C1923T between the asthma and control groups (P=0.033). The frequency of IL13 C1923T T/T in the Mauritian Indian asthma group was significantly higher than in the control group [odds ratio (OR)=2.119, 95% confidence interval=1.048-4.285]. The Chinese Han children with asthma had significantly higher frequencies of MS4A2 C-109T T/T (OR=1.961, P=0.001) and ADRB2 R16G A/A (OR=2.575, P=0.000) than the control group. The IL13 C1923T locus predisposed to asthma in Mauritian Indian children, which represents an ethnic difference from the Chinese Han population. The MS4A2 C-109T T/T and ADRB2 R16G A/A genotypes were associated with asthma in the Chinese Han children.
Assuntos
Povo Asiático/genética , Asma/genética , Predisposição Genética para Doença/etnologia , Polimorfismo de Nucleotídeo Único/genética , Adolescente , Asma/epidemiologia , Asma/etnologia , Estudos de Casos e Controles , Causalidade , Criança , Pré-Escolar , China/epidemiologia , China/etnologia , Feminino , Estudos de Associação Genética , Loci Gênicos , Predisposição Genética para Doença/epidemiologia , Genótipo , Humanos , Interleucina-13/genética , Interleucina-4/genética , Subunidade alfa de Receptor de Interleucina-4/genética , Masculino , Maurício/epidemiologia , Maurício/etnologia , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase em Tempo Real , Receptores Adrenérgicos beta 2/genética , Receptores de IgE/genética , Adulto JovemRESUMO
Our objective was to investigate the distributions of six single nucleotide polymorphisms (SNPs) MS4A2 E237G, MS4A2 C-109T, ADRB2 R16G, IL4RA I75V, IL4 C-590T, and IL13 C1923T in Mauritian Indian and Chinese Han children with asthma. This case-control association study enrolled 382 unrelated Mauritian Indian children, 193 with asthma and 189 healthy controls, and 384 unrelated Chinese Han children, 192 with asthma and 192 healthy controls. The SNP loci were genotyped using polymerase chain reaction (PCR)-restriction fragment length polymorphism for the Chinese Han samples and TaqMan real-time quantitative PCR for the Mauritian Indian samples. In the Mauritian Indian children, there was a significant difference in the distribution of IL13 C1923T between the asthma and control groups (P=0.033). The frequency of IL13 C1923T T/T in the Mauritian Indian asthma group was significantly higher than in the control group [odds ratio (OR)=2.119, 95% confidence interval=1.048-4.285]. The Chinese Han children with asthma had significantly higher frequencies of MS4A2 C-109T T/T (OR=1.961, P=0.001) and ADRB2 R16G A/A (OR=2.575, P=0.000) than the control group. The IL13 C1923T locus predisposed to asthma in Mauritian Indian children, which represents an ethnic difference from the Chinese Han population. The MS4A2 C-109T T/T and ADRB2 R16G A/A genotypes were associated with asthma in the Chinese Han children.
Assuntos
Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Adulto Jovem , Povo Asiático/genética , Asma/genética , Predisposição Genética para Doença/etnologia , Polimorfismo de Nucleotídeo Único/genética , Asma/epidemiologia , Asma/etnologia , Estudos de Casos e Controles , Causalidade , China/epidemiologia , China/etnologia , Estudos de Associação Genética , Loci Gênicos , Genótipo , Predisposição Genética para Doença/epidemiologia , /genética , /genética , /genética , Maurício/epidemiologia , Maurício/etnologia , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase em Tempo Real , /genética , Receptores de IgE/genéticaRESUMO
Recent evidence has suggested that single-nucleotide polymorphisms (SNPs) located at 5p15.33 contribute to susceptibilities for several cancer types, including prostate cancer. To determine whether SNP rs402710 in this region plays a role in prostate cancer, we analyzed these associations in a Chinese population; 251 prostate cancer patients and 273 control subjects were included in this case-control study. Genotypes were determined by PCR-RFLP. We found that subjects carrying the CC homozygote had a decreased risk for prostrate cancer compared to those carrying TT/TC genotypes (odds ratio (OR) = 0.69, 95% confidence interval (CI) = 0.48-0.98, P = 0.038). Compared with the TT homozygote, subjects carrying the CC homozygote also had a decreased risk for prostate cancer (OR = 0.71, 95%CI = 0.51-0.99, P = 0.043). We conclude that rs402710 polymorphisms in the 5p15.33 region are associated with prostate cancer risk in the Chinese population. Further investigations with large cohorts and done worldwide are warranted to determine whether our findings are detected in other populations.