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Benzene exposure is known to cause serious damage to the human hematopoietic system. However, recent studies have found that chronic benzene exposure may also cause neurological damage, but there were few studies in this issue. The aim of this study was to investigate the mechanism of damage to the central nervous system (CNS) by chronic benzene exposure with a multi-omics analysis. We established a chronic benzene exposure model in C57BL/6J mice by gavage of benzene-corn oil suspension, identified the differentially expressed proteins (DEPs) and differentially expressed genes (DEGs) in mice brain using 4D Label-free proteomic and RNA-seq transcriptomic. We observed that the benzene exposure mice had a significant loss of body weight, reduction in complete blood counts, abnormally high MRI signals in brain white matter, as well as extensive brain edema and neural demyelination. 162 DEPs were identified by the proteome, including 98 up-regulated and 64 down-regulated proteins. KEGG pathway analysis of DEPs showed that they were mainly involved in the neuro-related signaling pathways such as metabolic pathways, pathways of neurodegeneration, chemical carcinogenesis, Alzheimer disease, and autophagy. EPHX1, GSTM1, and LIMK1 were identified as important candidate DEGs/DEPs by integrated proteomic and transcriptomic analyses. We further performed multiple validation of the above DEGs/DEPs using fluorescence quantitative PCR (qPCR), parallel reaction monitoring (PRM), immunohistochemistry, and immunoblotting to confirm the reliability of the multi-omics study. The functions of these DEGs/DEPs were further explored and analyzed, providing a theoretical basis for the mechanism of nerve damage caused by benzene exposure.
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OBJECTIVE: To observe the expression of phosphatase and tensin homology deleted on chromosome ten (PTEN) in myocardial tissue in patients with coronary heart disease, and explore the relevance between the expression of PTEN and the occurrence and development of coronary heart disease. METHODS: A total of 16 death cases with pathological diagnosis of coronary heart disease were collected as experimental group, and 19 cases without myocardial lesions were selected as control group. The expression of PTEN protein and its mRNA were detected by immunohistochemistry and real-time fluorescence quantitative PCR respectively. The correlation between the expression of PTEN and the pathogenesis of coronary heart disease was analyzed. RESULTS: The expression of PTEN protein in myocardium in cases with coronary heart disease was significantly lower compared with the control group (P < 0.05). There was no statistical difference of the expression of PTEN mRNA between experimental and control group (P > 0.05). CONCLUSION: PTEN may be involved in the occurrence and development of coronary heart disease.
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Doença da Artéria Coronariana/patologia , Miocárdio/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Doença da Artéria Coronariana/metabolismo , Humanos , RNA Mensageiro/metabolismoRESUMO
Growing evidence has indicated that polymorphism present in the miRNA binding site of target gene can alter the ability of miRNAs to bind its target gene and modulate the development and progression of cancer. We aimed to investigate the association between let-7 KRAS rs712 polymorphism and the risk of colorectal cancer (CRC). The let-7 KRAS rs712 was analyzed in a case-control study, including 339 CRC patients and 313 age- and sex-matched controls; the relationship between the polymorphism and the clinicopathological features of CRC was also examined. Individuals carrying the let-7 KRAS rs712 TT genotype and T allele had an increased risk of developing CRC (TT vs. GG, adjusted OR = 2.18; 95% CI, 1.00-4.77; T vs. G, adjusted OR = 1.50; 95% CI, 1.15-1.96). Stratified analyses revealed that CRC patients with the let-7 KRAS rs712 TT genotype were more likely to have clinical stage III or IV disease (OR = 3.29, 95% CI, 1.32-8.20) and distant metastasis (OR = 4.70, 95% CI, 1.81-12.25). These findings provide evidence that the let-7 KRAS rs712 polymorphism may play crucial roles in the etiology of CRC.
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Neoplasias Colorretais/genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Idoso , Alelos , Estudos de Casos e Controles , Neoplasias Colorretais/patologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Razão de Chances , Proteínas Proto-Oncogênicas p21(ras) , Risco , Carga TumoralRESUMO
BACKGROUND: For some common thyroid-related conditions with high prevalence and long follow-up times, ChatGPT can be used to respond to common thyroid-related questions. In this cross-sectional study, we assessed the ability of ChatGPT (version GPT-4.0) to provide accurate, comprehensive, compassionate, and satisfactory responses to common thyroid-related questions. STUDY DESIGN: First, we obtained 28 thyroid-related questions from the Huayitong app, which together with the two interfering questions eventually formed 30 questions. Then, these questions were responded to by ChatGPT (on July 19, 2023), junior specialist and senior specialist (on July 20, 2023) separately. Finally, 26 patients and 11 thyroid surgeons evaluated those responses on four dimensions: accuracy, comprehensiveness, compassion, and satisfaction. RESULTS: Among the 30 questions and responses, ChatGPT's speed of response was faster than that of the junior specialist (8.69 [7.53-9.48] vs. 4.33 [4.05-4.60], P <.001) and senior specialist (8.69 [7.53-9.48] vs. 4.22 [3.36-4.76], P <.001). The word count of the ChatGPT's responses was greater than that of both junior specialist (341.50 [301.00-384.25] vs. 74.50 [51.75-84.75], P <0.001) and senior specialist (341.50 [301.00-384.25] vs. 104.00 [63.75-177.75], P <0.001). ChatGPT received higher scores than junior specialist and senior specialist in terms of accuracy, comprehensiveness, compassion and satisfaction in responding to common thyroid-related questions. CONCLUSIONS: ChatGPT performed better than junior specialist and senior specialist in answering common thyroid-related questions, but further research is needed to validate the logical ability of the ChatGPT for complex thyroid questions.
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The miR-34 family members, described as potential tumor suppressors, were downregulated in colorectal cancer (CRC). Loss of miR-34 impairs TP53-mediated cell death, while overexpression of miR-34 induces apoptosis. A potentially functional polymorphism (i.e., rs4938723T/C) in the promoter region of pri-miR-34b/c was predicted to influence the GATA-X binding sites. We aimed to investigate the association between miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms and the risk of CRC. We genotyped the two polymorphisms in 347 CRC patients and 488 healthy controls using polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing assay. We found that the CC genotype and C allele of the miR-34b/c rs4938723 were associated with a significantly decreased risk of CRC compared with the TT genotype and T allele (CC vs. TT: adjusted OR=0.56; 95% CI, 0.34-0.91; C vs. T: adjusted OR=0.78; 95% CI, 0.64-0.97). In combined analysis, a borderline significance was also observed in subjects carrying the rs4938723 CT/CC and TP53 GG genotypes (adjusted OR=0.66; 95% CI, 0.43-0.99). These findings indicate that the rs4938723 in the promoter region of pri-miR-34b/c was a protective factor for the development of CRC. As the significance is marginal, further replication studies are warranted to confirm these results.
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Neoplasias Colorretais/genética , Variação Genética , MicroRNAs/genética , Regiões Promotoras Genéticas/genética , Neoplasias Colorretais/fisiopatologia , Feminino , Predisposição Genética para Doença , Humanos , Masculino , Polimorfismo de Nucleotídeo ÚnicoRESUMO
Recently, single nucleotide polymorphisms in let-7 miRNA binding site in 3' untranslated region (UTR) of KRAS mRNA have been found to be associated with the cancer risk. In this study, we genotyped the frequency of KRAS rs712 to test its effect on gastric cancer (GC) risk in a hospital-based case-control study in a Chinese population, with 181 histologically confirmed GC patients and 674 cancer-free controls, using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) assay. The TT genotype of rs712 was associated with an increased risk of GC when taking GG genotype as a reference (adjusted odds ratio (OR) = 3.05, 95 % confidence interval (CI), 1.53-6.08). Similarly, the T allele of rs712 was associated with a statistically significant increase in susceptibility compared with G allele (adjusted OR = 1.44, 95 % CI, 1.10-1.90). Our data demonstrated that the T allele of the let-7 binding site polymorphism rs712 in KRAS 3' UTR was associated with a significantly increased risk of GC, suggesting that the KRAS rs712 polymorphism may be a genetic marker for the development of GC.
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MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Neoplasias Gástricas/genética , Proteínas ras/genética , Regiões 3' não Traduzidas , Adulto , Idoso , Sítios de Ligação , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Proteínas Proto-Oncogênicas p21(ras) , Fatores de RiscoRESUMO
Several lines of evidence indicate that inflammatory processes play pivotal role in the development of intracranial aneurysm (IA). Recently, polymorphisms in the interleukin-12 (IL-12) gene were shown to be associated with immune-mediated inflammatory disease. The aim of this study was to investigate the interactions of IL-12A and IL-12B polymorphisms on the risk of IA in a Chinese population. A total of 422 individuals (including 164 patients with IA and 258 controls) were involved in the study. The polymorphisms (i.e., rs2243115 and rs568408 in IL-12A and rs3212227 in IL-12B) were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing. We found an association of the AC/CC genotypes and C allele of IL-12B rs3212227 with an increased risk of IA, compared with the AA genotype and A allele (AC/CC vs. AA: OR = 2.09, 95 % CI: 1.29-3.38; C vs. A: OR = 1.45, 95 % CI: 1.10-1.91). Moreover, a significant gene interaction of IL-12A and IL-12B was evident on the risk of IA, and subjects carrying variant genotypes of IL-12B rs3212227 had an increased risk of IA. In the stratified analysis by gender, the IL-12B rs3212227 AC/CC genotypes had an increased risk of IA compared with the AA genotype in male patients (AC/CC vs. AA: OR = 4.63, 95 % CI: 1.92-11.16). These findings suggest that the IL-12A and IL-12B independently and jointly be involved in the susceptibility to IA.
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Predisposição Genética para Doença , Subunidade p35 da Interleucina-12/genética , Subunidade p40 da Interleucina-12/genética , Aneurisma Intracraniano/genética , Polimorfismo de Nucleotídeo Único/genética , Estudos de Casos e Controles , Demografia , Feminino , Frequência do Gene/genética , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
C1qs are key components of the classical complement pathway. They have been well documented in human and mammals, but little is known about their molecular and functional characteristics in fish. In the present study, full-length cDNAs of c1qA, c1qB, and c1qC from zebrafish (Danio rerio) were cloned, revealing the conservation of their chromosomal synteny and organization between zebrafish and other species. For functional analysis, the globular heads of C1qA (ghA), C1qB (ghB), and C1qC (ghC) were expressed in Escherichia coli as soluble proteins. Hemolytic inhibitory assays showed that hemolytic activity in carp serum can be inhibited significantly by anti-C1qA, -C1qB, and -C1qC of zebrafish, respectively, indicating that C1qA, C1qB, and C1qC are involved in the classical pathway and are conserved functionally from fish to human. Zebrafish C1qs also could specifically bind to heat-aggregated zebrafish IgM, human IgG, and IgM. The involvement of globular head modules in the C1q-dependent classical pathway demonstrates the structural and functional conservation of these molecules in the classical pathway and their IgM or IgG binding sites during evolution. Phylogenetic analysis revealed that c1qA, c1qB, and c1qC may be formed by duplications of a single copy of c1qB and that the C1q family is, evolutionarily, closely related to the Emu family. This study improves current understanding of the evolutionary history of the C1q family and C1q-mediated immunity.
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Complemento C1q/metabolismo , Via Clássica do Complemento/fisiologia , Evolução Molecular , Filogenia , Proteínas de Peixe-Zebra/metabolismo , Peixe-Zebra/metabolismo , Animais , Complemento C1q/química , Complemento C1q/genética , Complemento C1q/imunologia , Escherichia coli , Hemólise , Humanos , Imunoglobulina G/química , Imunoglobulina G/genética , Imunoglobulina G/imunologia , Imunoglobulina G/metabolismo , Imunoglobulina M/química , Imunoglobulina M/genética , Imunoglobulina M/imunologia , Imunoglobulina M/metabolismo , Proteínas Recombinantes/química , Proteínas Recombinantes/genética , Proteínas Recombinantes/imunologia , Proteínas Recombinantes/metabolismo , Peixe-Zebra/genética , Peixe-Zebra/imunologia , Proteínas de Peixe-Zebra/química , Proteínas de Peixe-Zebra/genética , Proteínas de Peixe-Zebra/imunologiaRESUMO
Emerging evidence has shown that miRNAs participate in human carcinogenesis as tumor suppressors or oncogenes. Single nucleotide polymorphism (SNP) which located in the pre-miRNA may affect the processing and then influence the expression of mature miRNA. Previous studies yielded conflicting results as to the association of two common polymorphisms in pre-miRNAs (i.e. hsa-miR-146 rs2910164 and hsa-miR-196a2 rs11614913) with breast cancer. To derive a more precise effect on the association between these polymorphisms and breast cancer risk, we conducted a meta-analysis. Through retrieving PubMed for the period up to May 2010, a total of four studies were identified with 3,007 cases and 3,718 controls for has-miR-146a rs2910164 polymorphism and with 3,287 cases and 4,298 controls for hsa-miR-196a2 rs11614913 polymorphism. We found that individuals carrying CC genotype of has-miR-196a2 rs11614913 polymorphism was associated with an increased breast cancer risk in homozygote comparison (OR = 1.30; 95% CI, 1.01-1.68), and dominant model (OR = 1.11; 95% CI, 1.01-1.23). However, no significant association between has-miR-146a rs2910164 polymorphism and breast cancer risk was observed in all comparison models tested. These findings suggest that has-miR-196a2 rs11614913 polymorphism may play crucial roles in breast cancer development.
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Neoplasias da Mama/genética , Predisposição Genética para Doença , MicroRNAs/genética , Polimorfismo de Nucleotídeo Único , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Risco , Medição de RiscoRESUMO
Growing evidence suggests that RAD51 plays a pivotal role in the repair of DNA double-strand breaks and the maintenance of genomic stability. A single nucleotide polymorphism, 135G/C, has been identified in the 5' untranslated region of the RAD51 gene and has been shown to influence gene transcription activity. Previous studies yielded conflicting results as to the association of 135G/C polymorphism with breast cancer. We aimed to assess the effect of 135G/C of RAD51 on breast cancer susceptibility with the use of a meta-analysis. We performed a meta-analysis of 21 published case-control studies up to April 2010. We found that the CC genotype was associated with a significantly increased risk of breast cancer when compared with the GG, CG, and CG/GG genotypes. Subgroup analyses showed that individuals carrying the CC genotype were associated with an elevated tumor risk in European populations and in sporadic breast cancer. After stratified analyses according to manuscript quality, the CC genotype was associated with a significantly increased risk of breast cancer compared with the CG genotype in studies of both higher and lower quality. However, significantly elevated risk was found in studies of higher quality, but not in studies of lower quality when homozygote and a recessive comparison model were tested. This meta-analysis indicates that RAD51 135G/C polymorphism may be identified as a susceptibility locus for breast cancer.
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Neoplasias da Mama/genética , Polimorfismo Genético , Rad51 Recombinase/genética , Regiões 5' não Traduzidas , Estudos de Casos e Controles , Reparo do DNA , Marcadores Genéticos , Predisposição Genética para Doença , Genótipo , Humanos , Modelos Genéticos , Mutação , Polimorfismo de Nucleotídeo Único , Risco , Fatores de RiscoRESUMO
DNA mismatch repair, known as a fundamentally biological pathway, plays key roles in maintaining genomic stability, eliminating mismatch bases and preventing both mutagenesis in the short term and cancerogenesis in the long term. Polymorphisms of MLH1 in individuals may have an effect on the DNA repair capacity and therefore on cancer risk. Recently, emerging studies have been done to evaluate the association between MLH1 -93 G/A polymorphism and cancer risk in diverse populations. However, the results remain conflicting rather than conclusive. In this meta-analysis, we assessed reported studies of association between the MLH1 -93 G/A polymorphism and cancer risk including 13 691 cancer cases and 14 068 controls from 17 published studies. A borderline significant association between the MLH1 -93 G/A polymorphism and cancer risk was observed in overall analysis [heterozygote: odds ratio (OR) = 1.15; 95% confidence interval (CI) 1.05-1.26; homozygote: OR = 1.21; 95% CI, 1.04-1.40; dominant model: OR = 1.13; 95% CI 1.01-1.26; recessive model: OR = 1.21; 95% CI 1.07-1.35, respectively]. In subgroup analysis by ethnicity, significantly increased risks were found in Asian population and mixed population but not in Caucasian population. After stratified analysis according to the quality of literature, increased cancer risks were observed in the studies of lower quality but not in the studies of higher quality. Similarly, elevated cancer risks were observed in hospital-based studies but not in population-based studies. These findings showed no persuasive evidence that MLH1 -93 G/A polymorphism was associated with an increased risk of cancer. On the conservative standpoint, well-designed population-based studies with larger sample size in different ethnic groups should be performed to further confirm these results.
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Proteínas Adaptadoras de Transdução de Sinal/genética , Reparo de Erro de Pareamento de DNA , Predisposição Genética para Doença , Neoplasias/genética , Proteínas Nucleares/genética , Polimorfismo de Nucleotídeo Único , Frequência do Gene , Heterogeneidade Genética , Humanos , Proteína 1 Homóloga a MutL , Viés de Publicação , RiscoRESUMO
Genetic factors are known to be important in the development of esophageal squamous cell carcinoma (ESCC). Epidermal growth factor (EGF) can activate several signaling pathways leading to proliferation, differentiation, and tumorigenesis of epithelial tissues by binding with its receptor. Interindividual variations in EGF production were genetically contributed to EGF +61 G/A polymorphism. The purpose of this study is to investigate the potential association between EGF gene polymorphism and ESCC in a Chinese population. In this study, we analyzed single nucleotide polymorphism of EGF +61 G/A in 158 patients with ESCC and 212 age- and sex-matched controls in a Chinese population using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing. The variant genotypes of GA/AA were associated with a significantly decreased risk of ESCC compared with the wild-type homozygote GG (OR = 0.657, 95% CI: 0.434-0.996). However, no significant difference was observed between the EGF +61 G/A polymorphism and the risk of ESCC when the analyses were stratified in terms of age, gender, smoking status, different clinical stage, and lymph node status. The EGF +61 G/A polymorphism is associated with ESCC in a Chinese population. Our data suggests that the EGF gene may play a role in the development of ESCC.
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Carcinoma de Células Escamosas/genética , Fator de Crescimento Epidérmico/genética , Neoplasias Esofágicas/genética , Predisposição Genética para Doença , Polimorfismo de Nucleotídeo Único , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Polimorfismo de Fragmento de RestriçãoRESUMO
OBJECTIVE: To examine the expression of Sjögren's syndrome antigen B (SSB) gene in rats with early ischemic myocardium. METHODS: Adult healthy Sprague-Dawley rats were randomly divided into four groups (ischemia (MI), non-ischemia (NI), sham-operated (SO) and normal control (NO) groups). The expression of SSB and beta-actin gene in the myocardium was examined by real time PCR at 0 min, 5 min, 15 min, 30 min, 60 min, 120 min after ligation of the left anterior descending coronary artery (LAD). RESULTS: The expression of SSB gene was down-regulated after ischemia. Significantly lower expression of the gene in the rats with myocardial ischemia was found at 120 min after ligation compared with those before ligation and the control group at 120 min after ligation (P < 0.05 ). However, no significant differences were found between other groups (P > 0.05). CONCLUSION: SSB gene may be involved in the pathophysiologic regulating process in myocardial cells at the early stage of myocardial ischemia in rats.
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Autoantígenos/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Ribonucleoproteínas/metabolismo , Actinas/genética , Actinas/metabolismo , Animais , Autoantígenos/genética , Masculino , Isquemia Miocárdica/fisiopatologia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Ribonucleoproteínas/genética , Fatores de Tempo , Antígeno SS-BRESUMO
OBJECTIVE: To investigate the expression of Basigin mRNA in early ischemic myocardium (EIM) and non-ischemic myocardium (NIM) in rat. METHODS: Real-time polymerase chain reaction (PCR) technique was applied for detecting Basigin mRNA and beta-actin expression in EIM and NIM at 0 min, 15 min, 30 min, and 60 min. RESULTS: No significant differences of the Basigin mRNA expression in EIM and NIM between 0 min and sham operation (SO) or non-operation group (P > 0.05) were observed. Basigin mRNA expression in EIM significantly decreased in 15 min, 30 min, and 60 min group compared with that of 0 min group, respectively (P < 0.001). However, we failed to find any significant difference in NIM and NO from 0 min to 60 min. Basigin mRNA expression in EIM decreased significantly compared with that of in NIM (P < 0.05) after myocardial ischemia for 30 min. CONCLUSION: Basigin was involved in myocardium pathophysiology process after myocardial ischemia for 30 min, indicating that Basigin may be identified as a predictor of early myocardial ischemia in forensic medicine.
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Basigina/metabolismo , Proteínas Sanguíneas/metabolismo , Isquemia Miocárdica/metabolismo , Miocárdio/metabolismo , Animais , Basigina/genética , Proteínas Sanguíneas/genética , Medicina Legal , Masculino , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Fatores de TempoRESUMO
BACKGROUND: miRNA, as a biological marker, had more and more attention in recent years due to the important role it plays in cancer. Currently, there are extensive studies on miRNAs, among which miR-330-3p is reported to be implicated in the pathophysiological processes of various cancers. However, little progress has been made in the mechanism of miR-330-3p in gastric cancer. OBJECTIVE: To explore the expression and relevant mechanism of miR-330-3p and PRRX1 in gastric cancer (GC). METHODS: Forty-five GC patients (study group), from whom paired GC and paracancerous tissues were collected, and another 45 healthy subjects (control group) who underwent physical examination during the same period were enrolled. In addition, GC cells and human gastric mucosa cells were purchased, and miR-330-3p-mimics, miR-330-3p-inhibitor, miR-NC, si-PRRX1, and sh-PRRX1 were transfected into MKN45, SGC7901 cell. QRT-PCR was employed to assess the miR-330-3p and PRRX1 expressions in the samples, and the cell expressions of PRRX1, GSK-3ß, p-GSK-3ß, ß-catenin, p-ß-catenin, cyclin D1, N-cadherin, E-cadherin and vimentin were evaluated by Western blot (WB). MTT, Transwell and wound-healing experiments were adopted to detect cell proliferation, invasion and migration. RESULTS: MiR-330-3p was under-expressed, while PRRX1 was highly expressed in the serum of patients, both of which had an area under the curve (AUC) of more than 0.9. MiR-330-3p and PRRX1 were associated with tumor diameter, TNM staging, lymph node metastasis and differentiation of GC patients. Overexpression of miR-330-3p and inhibition of PRRX1 expression could suppress epithelial-mesenchymal transition (EMT), proliferation, invasion and apoptosis of cells. What is more, WB assay showed that overexpressed miR-330-3p and inhibited PRRX1 could inhibit the expression levels of p-GSK-3ß, ß-catenin, cyclin D1, N-cadherin and vimentin proteins, while elevating GSK-3ß, p-ß-catenin and E-cadherin protein expressions. Dual-luciferase reporter assay confirmed that there was a targeting relation between miR-330-3p and PRRX1. Furthermore, rescue experiments revealed that the cell proliferation, invasion, migration did not differ significantly between co-transfected miR-330-3p-mimics+sh-PRRX1, miR-330-3p-inhibitor+si-PRRX1 groups of MKN45 and SGC7901 and the miR-NC group (without transfected sequences). CONCLUSION: Overexpressed miR-330-3p can promote cell EMT, proliferation, invasion and apoptosis through inhibiting PRRX1-mediated Wnt/ß-catenin signaling pathway, which is expected to be a potential therapeutic target for GC.
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OBJECTIVE: To investigate the single nucleotide polymorphisms (rs3774963 C>G and rs11722146 A>G) of NFKB1 gene between the Chinese Han of Chengdu and Thai populations, and simultaneously to compare distributions of genotype and allelic frequencies of NFKB1 among different ethnic groups from the International Haplotype Map Project. METHODS: The genotypes and allele frequencies of NFKB1 gene rs3774963 C>G and rs11722146 A>G were analyzed in 118 healthy Chinese Han of Chengdu and 101 Thai individuals using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and DNA sequencing. RESULTS: The frequencies of the CC, CG, and GG genotypes of rs3774963 C>G were 15.3%, 43.2%, and 41.5% in Chinese Han of Chengdu, and 25.7%, 47.5%, and 26.7% in Thai population, respectively. The frequencies of the C and G alleles were 36.9% and 63.1% in Chinese Han of Chengdu, and 49.5% and 50.5% in Thai population, respectively. There were significant differences in the genotypes and allele frequencies between the two groups. The frequencies of the AA, AG, and GG genotypes of rs11722146 A>G were 22.9%, 50.0%, and 27.1% in Chinese Han of Chengdu, and 18.8%, 53.5%, and 27.7% in Thai population, respectively. The frequencies of the A and G alleles were 47.9%, 52.1% in Chinese Hen of Chengdu, and 54.5%, 45.5% in Thai population, respectively. However, no statistically significant difference was observed between the two populations. Interestingly, when compared with the data from the International Haplotype Map Project, the genotypes and allele frequencies of NFKB1 gene rs11722146 A>G but not rs3774963 C>G in the Chinese Han of Chengdu were significantly different from those among European and Sub-Saharan African populations. CONCLUSION: NFKB1 gene polymorphism in diverse populations is significantly different.
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Subunidade p50 de NF-kappa B/genética , Polimorfismo de Nucleotídeo Único , Sequência de Bases , China/etnologia , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , TailândiaRESUMO
BACKGROUND: Previous studies suggested that genetic polymorphisms in the epidermal growth factor receptor (EGFR) gene had been implicated in the susceptibility to some tumors and inflammatory diseases. EGFR has been recently implicated in vascular pathophysiological processes associated with excessive remodeling and atherosclerosis. Acute coronary syndrome (ACS) is a clinical manifestation of preceding atherosclerosis. Our purpose was to investigate the association of the EGFR polymorphism with the risk of ACS. In this context, we analyzed the HER-1 R497K and EGFR intron 1 (CA)n repeat polymorphisms in 191 patients with ACS and 210 age- and sex-matched controls in a Chinese population, using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) strategy and direct sequencing. RESULTS: There were significant differences in the genotype and allele distribution of R497K polymorphism of the EGFR gene between cases and controls. The Lys allele had a significantly increased risk of ACS compared with the Arg allele (adjusted OR = 1.49, 95% CI: 1.12-1.98, adjusted P = 0.006). However, no significant relationship between the number of (CA)n repeats of EGFR intron 1 (both alleles < 20 or any allele > or = 20) and the risk of ACS was observed (adjusted OR = 0.97, 95% CI: 0.58-1.64, adjusted P = 0.911). Considering these two polymorphisms together, there was no statistically significant difference between the two groups. CONCLUSION: R497K polymorphism of the EGFR gene is significantly associated with the risk of ACS. Our data suggests that R497K polymorphism may be used as a genetic susceptibility marker of the ACS.
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Síndrome Coronariana Aguda/genética , Receptores ErbB/genética , Genes erbB-1 , Predisposição Genética para Doença , Polimorfismo Genético , Adulto , Idoso , Estudos de Casos e Controles , China , Feminino , Frequência do Gene , Genótipo , Humanos , Íntrons , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da PolimeraseRESUMO
Previous studies have demonstrated that miR-34 family members are abnormally expressed in gastric cancer. Overexpression of the miR-34 family suppresses gastric carcinogenesis, whereas downregulation of the miR-34 family promotes tumorigenesis. p53 can bind to the promoter region of miR-34b/c, leading to an increase of miR-34b/c expression. Recently, a variant in the promoter region of pri-miR-34b/c (rs4938723) has been discovered, with the function of altering the binding efficiency of transcription factor GATA. The purpose of this study was to examine the role of the miR-34b/c rs4938723 and TP53 Arg72Pro polymorphisms in the susceptibility of gastric cancer. We analyzed the distribution of the two polymorphisms in 197 patients with gastric cancer and 289 age-, gender-, ethnicity-, and living area-matched controls using polymerase chain reaction-restriction fragment length polymorphism and DNA direct sequencing. We found that the CT and CT/CC genotypes of the miR-34b/c rs4938723 were associated with a significantly decreased risk of gastric cancer compared with the TT genotype (CT vs. TT: odds ratio [OR]=0.66; 95% confidence interval [95% CI], 0.45-0.97; and CT/CC vs. TT: OR=0.67; 95% CI, 0.47-0.97, respectively). Combined analysis showed that subjects carrying the miR-34b/c rs4938723 CT/CC and TP53 CG/CC genotypes had a 0.62-fold decreased risk to develop gastric cancer compared with subjects carrying the miR-34b/c rs4938723 TT and TP53 CG/CC genotypes (OR=0.62; 95% CI, 0.40-0.96). These findings suggest that the miR-34b/c rs4938723 may individually and jointly have a protective effect on the risk of gastric risk.
Assuntos
MicroRNAs/genética , Polimorfismo de Fragmento de Restrição , Neoplasias Gástricas/genética , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Proteína Supressora de Tumor p53/genéticaRESUMO
Nasopharyngeal carcinoma (NPC) is characterized by its highly invasive and metastatic features. Therefore, screening genetic biomarkers of NPC to achieve early diagnose would be of great value for NPC therapy. Single nucleotide polymorphisms in let-7 miRNA binding site in 3' untranslated region of KRAS mRNA have been found to be associated with various cancer risks. In this study, we genotyped the frequency of KRAS rs712 to test its effect on NPC risk in a hospital-based case-control study in a Chinese population, with 188 histologically confirmed NPC patients and 356 cancer-free controls, using polymerase chain reaction-restriction fragment length polymorphism assay. There was no significant difference in the genotype and allele frequencies of the rs712 polymorphism between the NPC patients and the control group (GT vs. GG, OR 0.83, 95% CI 0.57-1.21; TT vs. GG, OR 1.27, 95% CI 0.58-2.75). Our data suggest that the KRAS rs712 polymorphism in let-7 miRNA binding site has no association with NPC risk. Further experiments with larger sample size or other polymorphism sites are needed to verify the result, especially in different ethnic groups.
Assuntos
MicroRNAs/genética , Neoplasias Nasofaríngeas/genética , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas/genética , Proteínas ras/genética , Regiões 3' não Traduzidas , Adulto , Povo Asiático/genética , Sítios de Ligação , Carcinoma , Estudos de Casos e Controles , Feminino , Frequência do Gene , Predisposição Genética para Doença , Humanos , Masculino , Pessoa de Meia-Idade , Carcinoma Nasofaríngeo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Proto-Oncogênicas p21(ras) , Proteínas ras/metabolismoRESUMO
Evidence has suggested that tumour necrosis factor α (TNFα) may be involved in the aetiology of schizophrenia, but the underlying association between TNFα-308G/A polymorphism (rs1800629) and schizophrenia risk is still ambiguous. This meta-analysis was performed to quantitatively summarise the evidence for such a relationship. Eligible studies were identified by searching PubMed, EMBASE, CNKI (China National Knowledge Infrastructure), CBM (Chinese Biomedical Literature Database) and WANFANG databases within a range of published years from 1990 to July 2012. The odds ratio (OR) corresponding to the 95% confidence interval (CI) was used to assess the different associations. Twenty-one studies with 4340 cases and 5745 controls were included in this meta-analysis. The pooled examination displayed that there was no significant association between TNFα-308G/A polymorphism and susceptibility to schizophrenia overall (OR=1.047, 95% CI=0.876-1.253, P=0.614 for A vs. G), and no difference in Caucasian subgroup (OR=1.041, 95% CI=0.815-1.331, P=0.747) and Asian subgroup (OR=1.057, 95% CI=0.807-1.386, P=0.686). Lack of association was also found in males (OR=0.862, 95% CI=0.413-1.797, P=0.692) and females (OR=0.797, 95% CI=0.579-1.097, P=0.163) with a dominant model. Taken together, this meta-analysis suggests that TNFα-308G/A polymorphism may not be associated with schizophrenia susceptibility.