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Novel diagnostic and prognostic biomarkers of cancers are needed to improve precision medicine. Circular RNAs act as important regulators in cancers at the transcriptional and posttranscriptional levels. The circular RNA circMAN1A2 is highly expressed in nasopharyngeal carcinoma according to our previous RNA sequencing data; however, the expression and functions of circMAN1A2 in cancers are still obscure. Therefore, in this study, we evaluated the expression of circMAN1A2 in the sera of patients with nasopharyngeal carcinoma and other malignant tumors and analyzed its correlations with clinical features and diagnostic values. The expression levels of circMAN1A2 were detected by quantitative real-time PCR, and the correlations of clinical features with circMAN1A2 expression were analyzed by χ2 tests. Receiver operating characteristic curves were used to evaluate the clinical applications of circMAN1A2. The results showed that circMAN1A2 was upregulated in nasopharyngeal carcinoma, oral cancer, thyroid cancer, ovarian cancer, and lung cancer, with areas under the curves of 0.911, 0.779, 0.734, 0.694, and 0.645, respectively, indicating the good diagnostic value of circMAN1A2. Overall, our findings suggested that circMAN1A2 could be a serum biomarker for malignant tumors, providing important insights into diagnostic approaches for malignant tumors. Further studies are needed to elucidate the mechanisms of circMAN1A2 in the pathogenesis of cancer.
Assuntos
Biomarcadores Tumorais/sangue , Neoplasias/genética , RNA/genética , Regulação para Cima , Biomarcadores Tumorais/genética , Detecção Precoce de Câncer , Feminino , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/genética , Masculino , Neoplasias Bucais/sangue , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/genética , Carcinoma Nasofaríngeo/sangue , Carcinoma Nasofaríngeo/diagnóstico , Carcinoma Nasofaríngeo/genética , Neoplasias/sangue , Neoplasias/diagnóstico , Neoplasias Ovarianas/sangue , Neoplasias Ovarianas/diagnóstico , Neoplasias Ovarianas/genética , RNA Circular , Curva ROC , Reação em Cadeia da Polimerase em Tempo Real , Neoplasias da Glândula Tireoide/sangue , Neoplasias da Glândula Tireoide/diagnóstico , Neoplasias da Glândula Tireoide/genética , Sequenciamento do ExomaRESUMO
Recent studies have shown that on one hand, tumors need to obtain a sufficient energy supply, and on the other hand they must evade the body's immune surveillance. Because of their metabolic reprogramming characteristics, tumors can modify the physicochemical properties of the microenvironment, which in turn affects the biological characteristics of the cells infiltrating them. Regulatory T cells (Tregs) are a subset of T cells that regulate immune responses in the body. They exist in large quantities in the tumor microenvironment and exert immunosuppressive effects. The main effect of tumor microenvironment on Tregs is to promote their differentiation, proliferation, secretion of immunosuppressive factors, and chemotactic recruitment to play a role in immunosuppression in tumor tissues. This review focuses on cell metabolism reprogramming and the most significant features of the tumor microenvironment relative to the functional effects on Tregs, highlighting our understanding of the mechanisms of tumor immune evasion and providing new directions for tumor immunotherapy.
Assuntos
Neoplasias/metabolismo , Neoplasias/patologia , Linfócitos T Reguladores/metabolismo , Microambiente Tumoral/fisiologia , Animais , Diferenciação Celular/fisiologia , Proliferação de Células/fisiologia , Humanos , Linfócitos T Reguladores/patologiaRESUMO
We study the heat generation in a quantum dot exposed to a rotating magnetic field and coupled to a normal lead. Both electron-phonon interaction and electron-electron interaction are considered in the dot. We show the emergence of resonances and antiresonances in the heat generation, which we attribute to constructive interference and destructive interference between phonon waves emitted from opposite spin channels in the dot.
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Actin filament-associated protein 1-antisense RNA1 (AFAP1-AS1), a cancer-related long non-coding RNA, has been found to be upregulated in multiple types of cancers. AFAP1-AS1 is important for the initiation, progression and poor prognosis of many cancers, including nasopharyngeal carcinoma (NPC). However, the mechanism underlying the regulation of AFAP1-AS1 expression is not well-understood. In our study, the potential promoter region of AFAP1-AS1 was predicted by comprehensive bioinformatics analysis. Moreover, promoter deletion analysis identified the sequence between positions -359 and -28 bp as the minimal promoter region of AFAP1-AS1. The ChIP assay results indicate that the AFAP1-AS1 promoter is responsive to the transcription factor c-Myc, which can promote high AFAP1-AS1 expression. This study is the first to clone and characterize the AFAP1-AS1 promoter region. Our findings will help to better understand the underlying mechanism of high AFAP1-AS1 expression in tumorigenesis and to develop new strategies for therapeutic high expression of AFAP1-AS1 in NPC.
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An increasing number of studies has confirmed that many cells can secrete vesicles or exosomes in eukaryotes, which contain important nucleic acids, proteins and lipids and play important roles in cell communication and tumor metastasis. This paper summarizes the comprehensive function of exosomal non-coding RNAs. Although some studies have shown that exosomes mediate tumor signal transduction, the functional mechanism of the tumor metastasis remains to be elucidated. In this paper, we reviewed the role of exosomal non-coding RNAs in mediating cancer metastasis in the tumor microenvironment to provide new ideas for the study of tumor pathophysiology.
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Nasopharyngeal carcinoma (NPC) is a particularly common malignant disease in areas of south China and Southeast Asia. To characterize the gene expression profiling of NPC, we detected the gene expression profiles in 22 NPC and 10 nontumor nasopharyngeal epithelial tissues by complementary DNA microarray. We identified 503 genes that were significantly (P < .001) differentially regulated between NPC and nontumor nasopharyngeal epithelial tissues. The differentially expressed genes are involved in many signaling pathways, such as the Wnt, transforming growth factor-beta, and mitogen-activated protein kinase signaling pathways. The aberrant expression of the Wnt signaling pathway components, such as wingless-type MMTV integration site family, member 5A, Frizzled homolog 7, casein kinase IIbeta, beta-catenin, CREB-binding protein, and Dishevelled-associated activator of morphogenesis 2 was validated on the NPC tissue microarrays. The data suggest that the Wnt signaling pathway may be abnormally regulated in NPC, which provides insight into the molecular mechanisms of NPC.
Assuntos
Perfilação da Expressão Gênica , Neoplasias Nasofaríngeas/patologia , Transdução de Sinais/genética , Proteínas Wnt/genética , Adolescente , Adulto , Idoso , Proteína de Ligação a CREB/genética , Proteína de Ligação a CREB/metabolismo , Caseína Quinase II/genética , Caseína Quinase II/metabolismo , Análise por Conglomerados , Feminino , Receptores Frizzled/genética , Receptores Frizzled/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Hibridização In Situ , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/genética , Neoplasias Nasofaríngeas/fisiopatologia , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Proteínas Proto-Oncogênicas/genética , Proteínas Proto-Oncogênicas/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Transdução de Sinais/fisiologia , Proteínas Wnt/metabolismo , Proteína Wnt-5a , beta Catenina/genética , beta Catenina/metabolismoRESUMO
Nasopharyngeal carcinoma (NPC) poses one of the serious health problems in southern Chinese, with an incidence rate ranging from 15 to 50/100,000. Chromosome translocation t(1;3) and frequent loss of heterogeneity on short arms of chromosome 3 and 9 have been reported to be associated with NPC, and a genome-wide scan identified an NPC susceptibility locus on chromosome 4p15.1-q12 recently. In our study, we collected samples from 18 families at high risk of NPC from the Hunan province in southern China, genotyped with a panel of polymorphic markers on short arms of chromosomes 3, 9, and 4p15.1-q12. A locus on 3p21 was identified to link to NPC with a maximum logarithm of odds for linkage score of 4.18. Fine mapping located the locus to a 13.6-cM region on 3p21.31-21.2, where a tumor suppressor gene cluster resided. Our findings identified a novel locus for NPC and provided a map location for susceptibility genes candidates. In contrast to a recent study, no significant evidence for NPC linkage to chromosomes 4 and 9 was observed.
Assuntos
Cromossomos Humanos Par 3/genética , Ligação Genética , Predisposição Genética para Doença , Neoplasias Nasofaríngeas/genética , China/epidemiologia , Mapeamento Cromossômico , Feminino , Genes Supressores de Tumor , Genótipo , Humanos , Escore Lod , Masculino , Repetições de Microssatélites , Família Multigênica , LinhagemRESUMO
OBJECTIVE: To analyze the expression and location of coding protein of UBAP1 gene and to understand the relationship between the expression pattern of the protein and cell carcinogenesis. METHODS: Bioinformatics was used to analyze the protein character to provide an available clue of subsequent research. The codon frame cDNA was amplified by PCR, and subcloned into enhance green fluorescence protein (EGFP) of pEGFP-C2. The recombinant plasmid was transfected into HNE1 cells. The expression of coding protein was observed by fluorescence microscopy. RESULTS: The expressed GFP-fusion protein generated striking green fluorescence in the cytoplasm in HNE1 cells. EGFP/UBAP1 was expressed and existed mainly in the nuclear, especially accumulated on the nuclear envelope. CONCLUSION: The expression difference in HNE1 might be related to the carcinogenesis of NPC.
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Neoplasias Nasofaríngeas/metabolismo , Proteínas de Neoplasias/biossíntese , Sequência de Bases , Proteínas de Transporte , Proteínas de Fluorescência Verde/biossíntese , Proteínas de Fluorescência Verde/genética , Humanos , Dados de Sequência Molecular , Proteínas de Neoplasias/genética , Proteínas Recombinantes/biossíntese , Proteínas Recombinantes/genética , TransfecçãoRESUMO
Human connexin 26 gene (Cx26) has been considered a candidate suppressor gene in mammary epithelial cells. To explain regulatory mechanism of the Cx26, a DNase-1 hypersensitive 1.6 kb fragment upstream of the 5'-terminus of the gene was sequenced and assayed with CAT reporter system. The results showed that the 1.6 kb sequence had powerful promoter activity. The fragment contains two GT boxes (centering at -6158 and -6213 bp), and a TATA-less TTAAAA box (-6237/-6232 bp) which is the new promoter region of human Cx26.
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Nasopharyngeal carcinoma (NPC) is rare in most parts of the world, but prevalent in southern China. Recently, a NGX6 gene was cloned, which is located in the region of minimal heterozygosity deletion at 9p21.3-22.1 and is down-expressed in NPC. The latest results suggest that the NGX6 gene is a candidate tumor suppressor for NPC. A correlation study using 2 single-nucleotide polymorphisms (SNPs) within NGX6 gene by means of dynamic allele specific hybridization (DASH) was performed in 105 unrelated case subjects and 183 control subjects which matched to the NPC cases in age, sex and residence. Significant results were obtained for one SNP mark (rs879284), which was located at -237 bp 5' up-stream of NGX6 gene, and the relative risk of this SNP mark was 3.93 (genotype CT) and 2.27 (genotype TT). The result has proved again that NGX6 gene may play a certain role in oncogenesis and development of nasopharyngeal carcinoma. The SNP mark rs879284 may influence on the expression of NGX6 gene due to its location on chromosome.
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Neoplasias Nasofaríngeas/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , DNA de Neoplasias/genética , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neoplasias Nasofaríngeas/patologiaRESUMO
OBJECTIVE: To get the genotype and allele frequency distributions of 8 short tandem repeat (STR) loci on chromosome 3p (D3S1297, D3S1489, D3S1266, D3S1568, D3S1289, D3S1300, D3S1285 and D3S3681) in Chinese Han population in Hunan area. METHODS: Blood samples were collected from the random Han individuals in Hunan and the whole genomic DNA was extracted. STR loci were amplified by multiplex-PCR technique and genotyped by ABI 377 sequencer. RESULTS: Ninety-one alleles were detected, with frequencies ranging from 0.002 to 0.431, and these alleles constituted 312 genotypes. All the 8 loci met Hardy-Weinberg equilibrium. The statistical analysis of 8 STR loci showed the heterozygosity (H) >or= 0.729, the discrimination power (DP) >or= 0.725, the probabilities of paternity exclusion (PPE) >or= 0.596, and the polymorphic information content (PIC >or= 0.682). The result indicated that there was a significant difference between Han ethnic group and the white and the black. CONCLUSION: These results could serve as valuable data to enrich the Chinese genetic database and play an important role in Chinese population genetic and forensic medical application.
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Cromossomos Humanos Par 3/genética , Repetições de Microssatélites/genética , Polimorfismo Genético , Adulto , Alelos , China , Feminino , Frequência do Gene , Genótipo , Humanos , MasculinoRESUMO
OBJECTIVE: To investigate the relationship of nasopharyngeal carcinoma (NPC) with the high frequency allele imbalance locus D6S1581, and the NPC associated gene FBXO30 which is located near D6S1581. METHODS: Genescan was used to genotype D6S1581 of 12 NPC pedigrees, 85 sporadic NPC patients and 181 normal volunteers. Then parametric/nonparametric linkage analysis and association analysis were performed. RESULTS: D6S1581 was linked with NPC, a Lod score of 2.611436 (P=0.00245) was obtained, and a significant difference in allele frequency was observed between familial NPC and control (P<0.005). CONCLUSION: These results suggest that D6S1581 is highly associated with NPC, and there may be one or more NPC associated genes near D6S1581, including FBXO30.
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Predisposição Genética para Doença/genética , Repetições de Microssatélites/genética , Neoplasias Nasofaríngeas/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , China , Proteínas F-Box/genética , Feminino , Frequência do Gene , Ligação Genética , Humanos , Masculino , Pessoa de Meia-Idade , LinhagemRESUMO
OBJECTIVE: To search novel SNPs in exons and regulatory regions of CDKN2A and two novel putative tumor suppressor genes NGX6 and UBAP1, which all reside on chromosome 9p21-22. METHODS: The exons and regulatory regions of those genes were amplified and sequenced in 96 subjects. RESULTS: Two novel SNPs were found, one resides on the sixth exon of UBAP1 gene and the other on the fourth exon of CDKN2A gene. Two novel SNPs were submitted to the dbSNP database, and their access ID are rs3135929 and rs3088440. The polymorphic information contents of them are 0.102 and 0.213 respectively. There is linkage equilibrium between them, and the polymorphic information content of their haplotype is 0.302, higher than any of them individually. CONCLUSION: The polymorphic information content can be improved by using haplotype analysis of several SNPs.
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Povo Asiático/genética , Proteínas de Transporte/genética , Cromossomos Humanos Par 9/genética , Genes p16/fisiologia , Proteínas de Membrana/genética , Polimorfismo de Nucleotídeo Único , Proteínas Supressoras de Tumor/genética , Sequência de Bases , China/etnologia , Predisposição Genética para Doença , Humanos , Polimorfismo Genético , Análise de Sequência de DNARESUMO
To get genotype and allele frequency distributions of seven short tandem repeat (STR) loci of chromosome 9p,D9S288,D9S157,D9S1748,D9S171,D9S161,D9S1817 and D9S1805 in Chinese Han population in Hunan area,blood samples were collected from the random Han individual in Hunan and the whole genomic DNA was extracted.STR loci were amplified by multiplex-PCR technique and genotyped by ABI 377 sequencer.Seventy-five alleles were detected,with frequencies ranging from 0.002 to 0.800,and constituted 243 genotypes. All the seven loci met Hardy-Weinberg equilibrium. The statistical analysis of seven STR loci showed H(heterozygosity) ranging from 0.347 to 0.844,DP(discrimination power) ranging from 0.346 to 0.841,PPE(probabilities of paternity exclusion) ranging from 0.308 to 0.738 and PIC(polymorphic information content) ranging from 0.328 to 0.822. The result indicated that there was a significant difference between Han ethnic group and the white and the black.
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Carcinoma Nasofaríngeo/imunologia , Carcinoma Nasofaríngeo/metabolismo , Neoplasias Nasofaríngeas/imunologia , Neoplasias Nasofaríngeas/metabolismo , Autoantígenos/metabolismo , Proteínas de Ligação a Ácido Graxo , Glicoproteínas/metabolismo , Humanos , Imunidade Inata/imunologia , Lactoferrina/metabolismo , Fosfoproteínas/metabolismo , Proteínas/metabolismoRESUMO
A single nucleotide polymorphism (SNP) is the most common type of genetic variation, and millions of SNPs have been documented so far. Because of dense distribution of SNPs across the genome, SNPs are viewed as ideal markers for research use in the post-genomic era. The application of the high-density whole genome-wide SNP array not only leads to more rapid, economical, and high throughput genotyping but also makes the investigation of the genetic variety or change in global patterns possible. The SNP array will be widely used in various research fields, such as large-scale genome-wide linkage and association studies to discover susceptibility genes in cancer, and loss of heterozygosity analysis to discover tumor suppressor genes and tumor molecular markers, and so on.
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Genoma Humano , Neoplasias/genética , Análise de Sequência com Séries de Oligonucleotídeos/métodos , Polimorfismo de Nucleotídeo Único , Predisposição Genética para Doença/genética , Humanos , Desequilíbrio de Ligação , Perda de HeterozigosidadeRESUMO
Current rectification effect in an asymmetric molecule HCOO-C6H4-(CH2)n sandwiched between two aluminum electrodes has been studied using an ab initio nonequilibrium Green's function method. The conductance of the system decreases exponentially with the increasing number n of CH2. The phenomenon of current rectification is observed such that a very small current appears at negative bias and a sharp negative differential resistance at a critical positive bias when n>or=2. The rectification effect arises from the asymmetric structure of the molecule and the molecule-electrode couplings. A significant rectification ratio of approximately 38 can be achieved when n=5.
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We previously identified a tissue-specific gene, short palate, lung, and nasal epithelium clone 1 (SPLUNC1), in nasopharyngeal epithelial tissues. SPLUNC1 was differentially expressed in nasopharyngeal carcinoma. Bioinformatic analysis revealed that SPLUNC1 has the bactericidal permeability-increasing protein/lipid-binding protein (BPI/LBP) domain and a 19 amino acid signal peptide, which suggest that it is a secretory protein. Its precise cellular localization in the respiratory tract is mainly in mucous cells and ducts of submucosal glands. However, little is known about its expression pattern in various human tissues. We generated a highly specific antibody and analyzed its distribution in the human fetus by immunohistochemistry to more precisely determine SPLUNC1 protein localization in human tissues. The results were further validated by RT-PCR. Our results showed that SPLUNC1 protein is expressed at not only the serous glands and epithelium of the upper respiratory tract and digestive tract, but also in the oculi of human embryos. Interestingly, we also found positive staining in fetus adipose tissue, a result not previously reported in studies of adult human tissues. Western blot analysis detected a 24 kDa SPLUNC1 protein in the compounds of nasopharyngeal secretions. This secretory protein was also detected in saliva and tears. Our research suggests that SPLUNC1 protein may not only be an antimicrobial peptide that plays an important role in the maintenance of homeostasis in the upper respiratory tract, oculi, and alimentary tract, it may also be important in the development and lipid metabolism of the adipose tissue.
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Feto/metabolismo , Glicoproteínas/metabolismo , Fosfoproteínas/metabolismo , Tecido Adiposo/embriologia , Tecido Adiposo/metabolismo , Adulto , Sequência de Aminoácidos , Especificidade de Anticorpos , Sequência de Bases , Primers do DNA/genética , Sistema Digestório/embriologia , Sistema Digestório/metabolismo , Olho/embriologia , Olho/metabolismo , Feminino , Expressão Gênica , Glicoproteínas/genética , Glicoproteínas/imunologia , Humanos , Imuno-Histoquímica , Dados de Sequência Molecular , Fosfoproteínas/genética , Fosfoproteínas/imunologia , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Sistema Respiratório/embriologia , Sistema Respiratório/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Distribuição TecidualRESUMO
To elucidate the molecular pathogenesis of nasopharyngeal carcinoma, the information of genes and literature related to nasopharyngeal carcinoma were enquired. Using Microsoft Access 2000, a simple database was established, which included the genes and literature related to nasopharyngeal carcinoma. According to the information of genes and literature, the molecular pathogenesis and the signal transduction pathway of nasopharyngeal carcinoma were preliminarily described in this paper.
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Bases de Dados Bibliográficas , Bases de Dados Genéticas , Neoplasias Nasofaríngeas/genética , Genes p53 , Humanos , Neoplasias Nasofaríngeas/etiologia , Transdução de SinaisRESUMO
BACKGROUND & OBJECTIVE: Poly-l-lysine-modified silica nanoparticle(PMS-NP) was a novel non-viral vector for gene delivery. The current study was designed to evaluate the biocompatibility of PMS-NP for its further utilization in vivo. METHODS: Cell transfection and flow cytometry were used to elucidate the delivery efficiency of plasmid DNA and antisense ODN mediated by PMS-NP in the presence of serum-containing medium. Subsequently, the biocompatibility of PMS-NP in vivo was evaluated using filtration assay of plasma proteins and erythrocyte aggregation assay. RESULTS: The abilities of PMS-NP to deliver plasmid DNA and antisense ODN in vitro clearly decreased in the presence of serum-containing medium. PMS-NP/DNA(ODN)complexes bound plasma proteins and triggered erythrocyte aggregation. CONCLUSION: PMS-NP might interact with plasma proteins, resulting in decreased transfection efficiency in vitro. And filtration assay of plasma proteins and the erythrocyte aggregation assay demonstrated that the interaction of PMS-NP with plasma proteins and erythrocytes might play a negative role in gene transfection efficiency in vivo. And its biocompatibility needs to be further improved.