RESUMO
The aim of this study was to screen for key biomarkers of osteosarcoma (OS) by tracking altered modules. Protein-protein interaction (PPI) networks of OS and normal groups were constructed and re-weighted using the Pearson correlation coefficient (PCC), respectively. The condition-specific modules were explored from OS and normal PPI networks using a clique-merging algorithm. Altered modules were identified by a maximum weight bipartite-matching method. The important biological pathways in OS were identified by a pathway-enrichment analysis using genes from disrupted modules. The most important genes in these pathways were selected as key biomarkers. Finally, the mRNA and protein expressions of hub genes in OS bone tissues were analyzed using reverse transcription-polymerase chain reaction and western blotting, respectively. We identified 703 and 2270 modules in normal and disease networks, respectively; 150 altered modules were identified from among these and explored. We identified 10 important pathways based on gene pairs with altered PCC > 1 in the disrupted modules (P < 0.01), and PCNA, ATP6V1C2, ATP6V1G3, FEN1, CDC7, and RPA3 (expressed in these pathways) were selected as key genes of OS. We observed that these genes (and the proteins they encoded) were differentially expressed between normal and OS samples (P < 0.01) (excluding ATP6V1C2, whose protein expression did not differ significantly). Therefore, we identified 5 gene signatures that may be potential biomarkers for the detection and effective therapy of OS.
Assuntos
Biomarcadores Tumorais/genética , Neoplasias Ósseas/genética , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Osteossarcoma/genética , Biomarcadores Tumorais/metabolismo , Neoplasias Ósseas/diagnóstico , Neoplasias Ósseas/metabolismo , Neoplasias Ósseas/patologia , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Endonucleases Flap/genética , Endonucleases Flap/metabolismo , Perfilação da Expressão Gênica , Humanos , Análise de Sequência com Séries de Oligonucleotídeos , Osteossarcoma/diagnóstico , Osteossarcoma/metabolismo , Osteossarcoma/patologia , Antígeno Nuclear de Célula em Proliferação/genética , Antígeno Nuclear de Célula em Proliferação/metabolismo , Mapeamento de Interação de Proteínas , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , ATPases Vacuolares Próton-Translocadoras/genética , ATPases Vacuolares Próton-Translocadoras/metabolismoRESUMO
PURPOSE: ZFP36 ring finger protein (ZFP36) and the suppressor of cytokine signaling 3 (SOCS3) have been reported to, respectively, regulate NF-κB and STAT3 signaling pathways. To better understand the correlation of NF-κB and STAT3 negative regulates pathway, we have investigated the involvement of ZFP36 and SOCS3 expressions in human prostate cancer (PCa). METHODS: In the present study, paired patient tissue microarrays were analyzed by immunohistochemistry, and the ZFP36 protein expression was quantitated as immunoreactive scores in patients with PCa. Associations between ZFP36/SOCS3 expression and various clinicopathological features and prognosis of PCa patients were statistically analyzed based on the Taylor database. Then, the functions of ZFP36 and SOCS3 in cancerous inflammation were determined using qPCR and immunohistochemistry in vitro and in vivo. RESULTS: ZFP36 protein expression in PCa tissues was significantly lower than those in non-cancerous prostate tissues (P < 0.05). In mRNA level, ZFP36 and SOCS3 had a close correlation with each other (P < 0.01, Pearson r = 0.848), and its upregulation was both significantly associated with low Gleason score (P < 0.001 and P < 0.001, respectively), negative metastasis (P < 0.001 and P < 0.001, respectively), favorable overall survival (P < 0.001 and P < 0.05, respectively), and negative biochemical recurrence (P < 0.001 and P < 0.001, respectively). Functionally, LPS treatment could lead to the overexpression of ZFP36 and SOCS3 in vitro and vivo. CONCLUSIONS: Our data offer the convincing evidence for the first time that the aberrant expressions of ZFP36 and SOCS3 may be involved into the progression and patients' prognosis of PCa, implying their potentials as candidate markers of this cancer.
Assuntos
Biomarcadores Tumorais/análise , Neoplasias da Próstata/patologia , Proteína 3 Supressora da Sinalização de Citocinas/biossíntese , Tristetraprolina/biossíntese , Idoso , Idoso de 80 Anos ou mais , Animais , Intervalo Livre de Doença , Humanos , Imuno-Histoquímica , Inflamação/metabolismo , Inflamação/patologia , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase , Prognóstico , Modelos de Riscos Proporcionais , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/mortalidade , Ratos , Ratos Sprague-Dawley , Proteína 3 Supressora da Sinalização de Citocinas/análise , Análise Serial de Tecidos , Tristetraprolina/análiseRESUMO
The swine leukocyte antigen (SLA) complex harbors highly polymorphic gene clusters encoding glycoproteins that are involved in responses to vaccines, infectious disease, and production performance. Pigs with well-defined SLA class II genes are useful for the study of disease, immunology, and vaccines. In this study, we analyzed four SLA class II genes (SLA-DRA, SLA-DRB1, SLA-DQA, SLA-DQB1) in 22 founder Guizhou minipigs using a sequence-based typing method. Twelve alleles were detected, compared with the SLA class II allele sequences in the GenBank, and one of twelve alleles was found to be novel in Guizhou minipigs. There are four SLA II haplotypes, and one of them has been previously reported in Meishan pigs. Furthermore, based on sequence information of these alleles, we developed a simple SLA typing method implemented to SLA-typing for unknown offspring of Guizhou minipigs, relying on designed twelve sequence specific primers that could discriminate between each other. According to the combination of sequence-based typing and PCR-SSP, we were able to rapidly check SLA typing of Guizhou breeding stock and identified four SLA haplotypes in the herd. Therefore, SLA-defined Guizhou minipigs will be useful as animal models for xenotransplantation and immunological research.
Assuntos
Genes MHC da Classe II/genética , Haplótipos/genética , Antígenos de Histocompatibilidade Classe II/genética , Polimorfismo Genético/genética , Porco Miniatura/genética , Alelos , Animais , Cruzamento/métodos , Antígenos de Histocompatibilidade Classe I , SuínosRESUMO
Plant traits are important indices for regulating and controlling yield ability in soybean varieties. It is important to comprehensively study the quantitative trait locus (QTL) mapping for soybean plant traits, cloning related genes, and marker assistant breeding. In this study, 236 F2 generation plants and a derivative group were constructed by using Jiyu50 and Jinong18, obtained from Jilin Province. A total of 102 simple sequence repeat markers were used to construct a genetic linkage map. With 2 years of molecular and phenotypic data, QTL analyses and mapping were conducted for soybean maturity, plant height, main stem node, main stem branch, seed weight per plant, and more. Five main plant traits were analyzed via inclusive composite interval mapping using QTL IciMapping v2.2. Using one-dimensional scanning, a total of 30 QTLs were detected and distributed across 1 (A1), 4 (C2), and 12 (G). There were 9 linkage groups, including 16 major QTLs. Using two-dimensional scanning, 7 pairs of epistatic QTL interactions for maturity and plant height were detected in the soybean.
Assuntos
Mapeamento Cromossômico/métodos , Glycine max/genética , Locos de Características Quantitativas , Cromossomos de Plantas/genética , DNA de Plantas/análise , Ligação Genética , Hibridização Genética , Repetições de MicrossatélitesRESUMO
Seed number per pod is an important component of yield traits in soybean (Glycine max L.). In 2010, we identified a natural mutant with an increased number of four-seed pods from a soybean variety named 'Jinong 18' (JN18). Subsequent observations indicated that the trait was stably inherited. To identify and understand the function of genes associated with this mutant trait, we analyzed the genetic differences between the mutant (JN18MT01) and source variety (JN18) by transcriptome sequencing. Three types of tissues, axillary buds, unfertilized ovaries, and young pods at three different growth stages, V6, R1, and R3, were analyzed, respectively. The sequencing results yielded 55,582 expressed genes and 4183 differentially expressed genes (DEGs). Among these, the log2 ratio value of 162 DEGs was >10, and 13 DEGs had overlapping expression at three different growth stages. Comparisons of DEGs among three different growth stages yielded similar results in terms of the percentage of genes classified into each gene ontology (GO) category. DEGs were classified into 25 different functional groups in clusters of orthologous groups analysis. Proportions of the main functional genes differed significantly over developmental stages. A comparison of enriched pathways among the three developmental stages revealed that 646 unigenes were involved in 103 metabolic pathways. These results show that the development of four-seed pods is associated with a complex network involving multiple physiological and metabolic pathways. This study lays the foundation for further research on cloning and on the molecular regulation of genes related to the four-seed pod mutation.
Assuntos
Frutas/genética , Regulação da Expressão Gênica de Plantas , Glycine max/genética , Proteínas de Plantas/genética , Característica Quantitativa Herdável , Sementes/genética , Transcriptoma , Frutas/anatomia & histologia , Frutas/crescimento & desenvolvimento , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Ontologia Genética , Redes Reguladoras de Genes , Sequenciamento de Nucleotídeos em Larga Escala , Redes e Vias Metabólicas/genética , Anotação de Sequência Molecular , Mutação , Fenótipo , Proteínas de Plantas/metabolismo , Sementes/crescimento & desenvolvimento , Glycine max/anatomia & histologia , Glycine max/crescimento & desenvolvimentoRESUMO
A 56-year-old man presented with fevers up to 40°C and acute pain in the left upper quadrant. Full blood count was normal and biochemical tests revealed increased serum globulin. Abdominal ultrasound revealed hepatomegaly and splenomegaly with multiple enlarged lymph nodes in the neck, axilla, and inguinal regions. The bone marrow smear was negative. Splenectomy was performed and the pathology revealed splenic ischemic infarcts. Biopsy of one of the axillary lymph nodes revealed macrophages filled with leishmanias. The patient tested positive by the rk39 dipstick test. He was treated with sodium stibogluconate and showed full recovery.
Assuntos
Leishmaniose Visceral/diagnóstico , Leishmaniose Visceral/patologia , Linfonodos/patologia , Biópsia , Humanos , Leishmaniose Visceral/diagnóstico por imagem , Linfonodos/parasitologia , Masculino , Pessoa de Meia-Idade , UltrassonografiaRESUMO
Apolipoprotein A5 (APOA5) and C3 (APOC3) genes are involved in the PPAR lipid metabolism pathway and thus associated with elevated triglyceride levels. However, whether APOA5 and APOC3 genetic polymorphisms affect intramuscular fat deposition and other meat quality traits remains unknown in pigs. One hundred and seventy-one Kele pigs were sampled to investigate genetic variants in the APOA5 and APOC3 genes and their association with seven pork quality traits. We identified 5 single nucleotide polymorphisms (SNPs) in the promoter region of the APOA5 gene and 17 SNPs in the APOC3 gene. Linkage disequilibrium analysis revealed 5 complete linkage disequilibria among these 22 SNPs. We found that 10 SNPs were significantly correlated with meat quality traits, including the mutation A5/-769 in the APOA5 gene, which was significantly associated with cooked weight percentage, and 9 SNPs in the APOC3 gene that were significantly associated with drip loss rate, meat color value of longissimus dorsi muscle and shear force. Therefore, these SNP markers will be useful for marker-assisted selection for improved pork quality.
Assuntos
Apolipoproteínas A/genética , Apolipoproteínas C/genética , Carne/análise , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Sus scrofa/genética , Animais , Qualidade dos Alimentos , Frequência do Gene , Desequilíbrio de Ligação , Fenótipo , TriglicerídeosRESUMO
Polymorphisms of the major histocompatibility complex (MHC) have been linked to many diseases, especially autoimmune disorders. Previous studies have shown that genetic variants in MHC class III are associated with breast cancer. To determine if there is an association between MHC class III and breast cancer risk in the Chinese Han population, we carried out a hospital-based case-control study in Guangdong and Jiangsu Provinces, including 216 histologically confirmed breast cancer patients and 216 healthy controls. Nine SNP markers distributed in the class III-coding region were detected using the Sequenom MassARRAY(®) iPLEX System. Deviation from Hardy-Weinberg equilibrium was observed for seven SNPs. There was no significant association between these seven SNP variants and breast cancer in these Chinese women (unconditional logistic regression analysis). However, chr6_31697494 at BAT2, one of the seven SNPs, was found to be significantly associated with both ER- and PR-positive breast cancer. In addition, both chr6_31911109 at C6orf48 and chr6_31975605 at ZBTB12, another two of the seven SNPs, show relevance with ER-positive breast cancer. In conclusion, this is the first evidence that genetic polymorphisms in the MHC class III region are significantly associated with ER-positive breast cancer in the Han Chinese population.
Assuntos
Neoplasias da Mama/genética , Proteínas de Ligação a DNA/genética , Proteínas de Neoplasias/genética , Polimorfismo de Nucleotídeo Único , Proteínas/genética , Receptores de Estrogênio/metabolismo , Fatores de Transcrição/genética , Povo Asiático , Neoplasias da Mama/diagnóstico , Neoplasias da Mama/metabolismo , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Humanos , Pessoa de Meia-Idade , Prognóstico , RNA Longo não Codificante , Receptores de Progesterona/metabolismoRESUMO
Coilia mystus is the most important harvested fish species in China; it inhabits quite different water environments during the different life history stages. Populations of C. mystus have dropped sharply due to overharvesting and water pollution. We developed eight microsatellite loci in C. mystus for conservation genetics studies. These new markers were tested in 20 individuals from the Min River in ChangLe. The number of alleles ranged from 3 to 8, the expected heterozygosity from 0.621 to 0.853 and the observed heterozygosity from 0.473-0.800. Only two loci deviated significantly from Hardy-Weinberg expectations due to heterozygote deficiency. These primers may provide a tool for understanding demography and population structure of this economically important and threatened species.