RESUMO
BACKGROUND: The role of CXCL10 in progression and prognosis of colorectal cancer (CRC) has been studied for years, yet results remain controversial. AIM: This study aims to explore the relationship between CXCL10 and CRC progression and prognosis. METHODS: We evaluated plasma CXCL10 in CRC patients using ELISA. We also performed a meta-analysis of the associations between CXCL10 and overall survival (OS), disease-free survival (DFS), disease-specific survival (DSS), relapse-free survival (RFS), and clinicopathological features. Finally, correlations between CXCL10 and methylation or immune infiltration were performed using TCGA data. RESULTS: ELISA analysis showed that CXCL10 was associated with age, red blood cells, blood platelets, and blood urea nitrogen. A separate analysis of 3,763 patients from 24 studies revealed that there were significant associations between low CXCL10 expression and OS (HR 1.25, 95% CI 1.01-1.53), DFS (HR 1.65, 95% CI 1.17-2.34), and RFS (HR 1.43, 95% CI 1.20-1.71) in CRC. Additionally, downregulated CXCL10 expression was significantly correlated with age [odds ratio (OR) 1.31, 95% CI 1.13-1.52], metastasis (OR 1.34, 95% CI 1.11-1.63), recurrence (OR 1.46, 95% CI 1.16-1.83), tumor location (OR 1.88, 95% CI 1.58-2.24), differentiation (OR 0.57, 95% CI 0.35-0.93), microsatellite instability (OR 0.23, 95% CI 0.15-0.35), BRAF mutation (OR 1.62, 95% CI 1.25-2.08), p53 mutation (OR 0.28, 95% CI 0.16-0.47), and CIMP (OR 0.27, 95% CI 0.17-0.43). Furthermore, significant associations were observed between CXCL10 and methylation and immune infiltration. CONCLUSIONS: The study suggests that CXCL10 might be a potential target for the treatment of CRC. TRIAL REGISTRATION: NCT03189992. Registered 4 June 2017, https://www.clinicaltrials.gov/ct2/show/study/NCT03189992?term=NCT03189992&rank=1 .
Assuntos
Quimiocina CXCL10/sangue , Neoplasias Colorretais/sangue , Recidiva Local de Neoplasia/sangue , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Quimiocina CXCL10/genética , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Neoplasias Colorretais/cirurgia , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mutação , Recidiva Local de Neoplasia/patologia , Recidiva Local de Neoplasia/cirurgia , Valor Preditivo dos Testes , Taxa de SobrevidaRESUMO
Mareks disease (MD), a lymphoproliferative disorder of chickens caused by the MD virus (MDV), is economically significant. The resistance/susceptibility to MD is controlled by host genetics. The host response to different virus strains varies. The pathogenicity of REV-LTR deleted GX0101LTR MDV has been previously reported. However, the precise molecular mechanism of the response of chickens to GX0101LTR remains unclear. The current study aimed at identifying the genes and pathways involved in the response to GX0101LTR virus infection in specific pathogen-free chicken embryo fibroblast cells using global transcriptome analysis. A total of 1,633 genes associated with GX0101LTR infection were identified. Functional analysis showed that the cytokine-cytokine receptor interaction plays an important role in the response to GX0101LTR infection.
Assuntos
Animais , Embrião de Galinha , Doença de Marek/diagnóstico , Doença de Marek/embriologia , Transcriptoma/fisiologiaRESUMO
Mareks disease (MD), a lymphoproliferative disorder of chickens caused by the MD virus (MDV), is economically significant. The resistance/susceptibility to MD is controlled by host genetics. The host response to different virus strains varies. The pathogenicity of REV-LTR deleted GX0101LTR MDV has been previously reported. However, the precise molecular mechanism of the response of chickens to GX0101LTR remains unclear. The current study aimed at identifying the genes and pathways involved in the response to GX0101LTR virus infection in specific pathogen-free chicken embryo fibroblast cells using global transcriptome analysis. A total of 1,633 genes associated with GX0101LTR infection were identified. Functional analysis showed that the cytokine-cytokine receptor interaction plays an important role in the response to GX0101LTR infection.(AU)
Assuntos
Animais , Embrião de Galinha , Doença de Marek/diagnóstico , Doença de Marek/embriologia , Transcriptoma/fisiologiaRESUMO
Neurofibromatosis type 1, also known as NF1 or von Recklinghausen's disease, is a common neurocutaneous syndrome that presents with multiple café-au-lait patches, skinfold freckling, dermatofibromas, neurofibromas, and Lisch nodules. The mutations of the gene NF1, encoding the protein neurofibromin, have been identified as the cause of this disease. Here, we report a clinical and molecular study of a Chinese patient with multiple café-au-lait skin freckles, dermatofibroma, central and peripheral nervous system tumors, and bone abnormalities attributed to NF1. The patient showed >6 café-au-lait spots on the body and multiple dermatofibromas. A brain glioma and multiple nerve sheath tumors inside and outside the vertebral canal were identified by magnetic resonance imaging, which also showed multiple intercostal nerve schwannomas and hydrocephalies above the cerebellar tentorium. Talipes equinus was also apparent. A mutation analysis of the NF1 gene revealed a novel frameshift mutation in exon 43, consisting of a heterozygous deletion of four nucleotides (GAGA) between positions 6520 and 6523. No NF1 mutations were detected in the patient's parents or younger brother. These results extend the list of known mutations in this gene. The absence of the NF1 mutation in the healthy family members suggests that it is responsible for the NF1 phenotype. To our knowledge, this frameshift mutation represents a novel NF1 case, and may be associated with nervous system tumors and bone abnormalities.
Assuntos
Mutação da Fase de Leitura , Neurofibromatose 1/genética , Neurofibromina 1/genética , Adolescente , Osso e Ossos/anormalidades , Éxons , Humanos , Masculino , Neurofibromatose 1/diagnósticoRESUMO
Heterosis has greatly contributed to conventional plant breeding and is widely used to increase crop plant productivity. However, although some studies have explored the mechanisms of heterosis at the genomic and transcriptome level, these mechanisms still remain unclear. The growth and development of maize seedlings and immature embryos have an important impact on subsequent production. This study investigated differentially expressed genes (DEGs) between parents and reciprocal hybrids in the seedling leaves, roots, and immature embryo 15 days after pollination using amplified fragment length polymorphism (AFLP)-based transcript profiling (cDNA-AFLP). We isolated 180, 170, and 108 genes from the leaves, roots, and immature embryos, respectively, that were differentially expressed between hybrids and parents. Sequencing and functional analysis revealed that 107 transcript-derived fragments in the roots and leaves and 90 in the immature embryos were involved in known functions, whereas many DEGs had roles in plant growth and development, photosynthesis, signal transduction, and seed germination. Quantitative reverse-transcription polymerase chain reaction analysis of relative expression levels between reciprocal hybrids and both parental genotypes of selected genes produced results that were consistent with cDNA-AFLP. We validated the expression patterns of 15 selected genes related to heterosis formation and revealed that most showed non-additive expression in one or both hybrids, including dominant, underdominant, and overdominant expression. This indicates that gene-regulatory interactions among parental alleles play an important role in heterosis during the early developmental stages of maize.
Assuntos
Quimera , Perfilação da Expressão Gênica , Hibridização Genética , Transcriptoma , Zea mays/genética , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Germinação/genética , Vigor Híbrido/genética , Endogamia , Reprodutibilidade dos TestesRESUMO
Recent studies have revealed that the inflammatory process plays a role in the pathogenesis of osteoarthritis (OA). The S100 family and receptor for advanced glycation end products (RAGE) participate in regulating inflammation, even in the production of matrix metalloproteinases (MMPs). MMP-1 degrades cartilage, which may result in OA development. Moreover, polymorphisms in RAGE, S100A8, and MMP-1 have a marked effect on ligand binding and transcription regulating. In this study, we investigated the potential genetic contribution of the RAGE, S100A8, and MMP-1 genes to OA. We performed a matched case-control association study and genotyped OA patients and healthy controls, who were analyzed by polymerase chain reaction-restriction fragment length polymorphism assays. A total of 207 patients were diagnosed with knee OA and underwent total knee replacement. The control group included 207 individuals who had standard X-rays of the knee joints to confirm K/L < 2 and were matched by age and gender. Single-nucleotide polymorphisms in RAGE (-429T/C, -374T/A, and 557G/A), S100A8 (rs3795391A/G), and MMP-1 (-1607 1G/2G, -755G/T, and -519A/G) were evaluated. RAGE -374T/A, S100A8 rs3795391A/G, MMP-1 -1607 1G/2G, -755G/T, and -519A/G showed no significant difference between OA patients and healthy controls. RAGE -429T/C and 557G/A showed a significant association between OA patients and healthy controls (P = 0.016 and 0.047, respectively). In haplotype analyses, no RAGE and MMP-1 haplotypes showed associations with OA. Our results suggest that the investigated polymorphism in the RAGE gene play a role in OA in the Han Chinese population.
Assuntos
Povo Asiático/genética , Etnicidade/genética , Predisposição Genética para Doença , Osteoartrite do Joelho/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor para Produtos Finais de Glicação Avançada/genética , Índice de Gravidade de Doença , Idoso , Calgranulina A/genética , Estudos de Casos e Controles , Feminino , Estudos de Associação Genética , Haplótipos/genética , Humanos , Masculino , Metaloproteinase 1 da Matriz/genéticaRESUMO
Matricaria recutita (L.), commonly known as chamomile, is one of the most valuable medicinal plants because it synthesizes a large number of pharmacologically active secondary metabolites known as α-bisabolol and chamazulene. Although the plant has been well characterized in terms of chemical constituents of essential oil as well as pharmacological properties, little is known about the genes responsible for biosynthesis of these compounds. In this study, we report a new full-length cDNA encoding farnesyl diphosphate synthase (FPS), a key enzyme in the pathway of biosynthesis of isoprenoids, from M. recutita. The cDNA of MrFPS comprises 1032 bp and encodes 343 amino acid residues with a calculated molecular mass of 39.4 kDa. The amino acid sequence homology and phylogenetic analysis indicated that MrFPS belongs to the plant FPS super-family and is closely related to FPS from the Asteraceae family. Expression of the MrFPS gene in Escherichia coli yielded FPS activity. Using real-time quantitative PCR, the expression pattern of the MrFPS gene was analyzed in different tissues of M. recutita as well as in response to methyl jasmonate. The expression analysis demonstrated that MrFPS expression varies in different tissues (with maximal expression in flowers and stems) and was significantly elevated in response to methyl jasmonate. This study will certainly enhance our understanding of the role of MrFPS in the biosynthesis and regulation of valuable secondary metabolites in M. recutita at a molecular level.
Assuntos
Acetatos/farmacologia , Ciclopentanos/farmacologia , Regulação da Expressão Gênica de Plantas/efeitos dos fármacos , Geraniltranstransferase/genética , Matricaria/enzimologia , Matricaria/genética , Oxilipinas/farmacologia , Regulação para Cima/efeitos dos fármacos , Sequência de Aminoácidos , Biocatálise/efeitos dos fármacos , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , Eletroforese em Gel de Poliacrilamida , Perfilação da Expressão Gênica , Genes de Plantas , Geraniltranstransferase/química , Geraniltranstransferase/isolamento & purificação , Matricaria/efeitos dos fármacos , Matricaria/crescimento & desenvolvimento , Dados de Sequência Molecular , Filogenia , Folhas de Planta/genética , Folhas de Planta/crescimento & desenvolvimento , Proteínas de Plantas/química , Proteínas de Plantas/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Reação em Cadeia da Polimerase em Tempo Real , Alinhamento de Sequência , Análise de Sequência de DNA , Transcrição Gênica/efeitos dos fármacos , Regulação para Cima/genéticaRESUMO
The insulin-like growth factor 2 receptor gene (IGF2R) encodes a transmembrane protein receptor and acts to sequester and degrade excess circulating insulin-like growth factor 2, which is critical for normal mammalian growth and development. Thus, IGF2R may serve as a candidate gene underlying growth trait in the common carp. In this study, we isolated the intron one of common carp IGF2R and detected the diversity in 3 continuous generations of FFRC strain common carp. A total of 8 loci were detected within this region, which were named in accordance with their location (i.e., Loc84, Loc106, Loc119, Loc130, Loc145, Loc163, Loc167, and Loc265). Loc106, Loc119, and Loc145 were moderately polymorphic; while Loc84, Loc130, Loc163, Loc167, and Loc265 exhibited slight level of polymorphism. However, significant differences between polymorphism information content values were not observed among the different generations. For Loc145, all generations deviated from Hardy-Weinberg equilibrium. The total number of significant linkage disequilibria for all generations equaled 40. Among them, 4 pairs were detected in each population, while 8 pairs were found in the 2nd and 3rd generations. For Loc130, the G/T genotype exhibited higher body weight when compared to that of the G/G genotype. The frequency of the homozygous G/G genotype reached 87.96%; thus, we can improve FFRC strain common carp growth performance by increasing the percentage of the G/T genotype within a breeding population. Therefore, the G/T genotype could be used as a molecular marker for superior growth traits.
Assuntos
Carpas/crescimento & desenvolvimento , Carpas/genética , Íntrons/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor IGF Tipo 2/genética , Animais , Peso Corporal/genética , Loci Gênicos , Heterozigoto , Desequilíbrio de Ligação/genética , Filogenia , Reação em Cadeia da PolimeraseRESUMO
Heat shock protein 90 (Hsp90) is one of the most abundant and conserved chaperone proteins and plays important roles in plant growth and responses to environmental stimuli. However, little is known regarding the sequence and function of Hsp90s in Matricaria recutita. In the present study, we cloned the full-length cDNA sequence of the hsp90 gene from this species. Using rapid amplification of cDNA ends technologies with 2 degenerate primers that were designed based on the hsp90 gene sequence from other members of Asteraceae, we isolated and characterized an Hsp90 homolog gene from M. recutita (Mr-Hsp90). The full-length Mr-hsp90 cDNA sequence, containing 2097 base pairs, encodes a protein of 698 amino acids. Based on amino acid sequence identity, Mr-Hsp90 showed high similarity to other cloned Hsp90 proteins. The Mr-Hsp90 protein was closely clustered with the Lactuca sativa in a phylogenetic tree. These results indicate that the cloned sequence of Mr-Hsp90 is a member of the Hsp90 family, which is reported for the first time in M. recutita. Next, we conducted a salt stress experiment to determine the protein's function under salt stress conditions. Survival of chamomile seedlings subjected to heat-shock pretreatment was significantly increased compared with groups that had not undergone heat-shock pretreatment in a salt stress environment. This indicates that Mr-Hsp90 plays an important role in the salt resistance of chamomile seedlings.
Assuntos
Clonagem Molecular/métodos , Proteínas de Choque Térmico HSP90/genética , Matricaria/metabolismo , Proteínas de Plantas/genética , Evolução Molecular , Proteínas de Choque Térmico HSP90/metabolismo , Resposta ao Choque Térmico , Matricaria/classificação , Matricaria/genética , Matricaria/crescimento & desenvolvimento , Filogenia , Proteínas de Plantas/metabolismo , Salinidade , Sementes/genética , Sementes/crescimento & desenvolvimento , Sementes/metabolismo , Alinhamento de Sequência , Análise de Sequência de DNARESUMO
Heterosis is the superior performance of heterozygous individuals and has been widely exploited in plant breeding, although the underlying regulatory mechanisms still remain largely elusive. To understand the molecular basis of heterosis in maize, in this study, roots and leaves at the seedling stage and embryos and endosperm tissues 15 days after fertilization of 2 elite hybrids and their parental lines were used to estimate the levels and patterns of cytosine methylation by the methylation-sensitive amplification polymorphism method. The relative total methylation levels were lower in all the tissues of all hybrids than their corresponding mid-parent values, and the number of demethylation events was higher in the hybrids. These results implied that the decreasing trend and demethylation in hybrids relative to their parents may enable the derepression and possibly expression of many genes that were associated with the phenotypic variation in hybrids. To further analyze the observed methylation pattern changes, a total of 63 differentially displayed DNA fragments were successfully sequenced. Basic Local Alignment Search Tool analysis showed that 11 fragments shared similarity with known functional proteins in maize or other plant species, including metabolism, transposon/retrotransposon, development, stress response, and signal transduction, which indicated that these genes might play a significant role in maize hybrid vigor.
Assuntos
Metilação de DNA , Regulação da Expressão Gênica de Plantas , Vigor Híbrido , Hibridização Genética , Zea mays/genética , EndogamiaRESUMO
Aralia elata is an important medicinal plant in China; it produces large amounts of oleanane type triterpene saponins. A full-length cDNA encoding ß-amyrin synthase (designated as AeAS) was isolated from young leaves of A. elata by reverse transcription-PCR. The full-length cDNA of AeAS was found to have a 2292-bp open reading frame, encoding a protein with 763 amino acid residues. The deduced amino acid sequence of AeAS showed the highest identity (97%) to Panax ginseng ß-amyrin synthase. When AeAS cDNA was expressed in Escherichia coli, an 87.8-kDa recombinant protein was detected by SDS-PAGE and Western blotting. The sequence was also heterologously expressed in the yeast Pichia pastoris, and production of ß-amyrin was detected by HPLC. Tissue expression pattern analysis by real-time reverse transcription-PCR revealed that AeAS is strongly expressed in leaves and stems, and weakly expressed in roots and flowers.
Assuntos
Aralia/enzimologia , Aralia/genética , Genes de Plantas/genética , Transferases Intramoleculares/genética , Plantas Medicinais/enzimologia , Plantas Medicinais/genética , Árvores/enzimologia , Sequência de Aminoácidos , Sequência de Bases , Western Blotting , Cromatografia Líquida de Alta Pressão , Clonagem Molecular , DNA Complementar/genética , Eletroforese em Gel de Poliacrilamida , Regulação da Expressão Gênica de Plantas , Transferases Intramoleculares/química , Dados de Sequência Molecular , Filogenia , Saponinas/biossíntese , Alinhamento de Sequência , Análise de Sequência de DNA , Árvores/genética , Triterpenos/metabolismoRESUMO
We studied whether two IGF2 transcripts in common carp are similar to those found in zebrafish. The full-length IGF2a cDNA contains a 5'-terminal untranslated region (UTR) of 105 bp, a 3'-terminal UTR of 1358 bp and an open reading frame of 612 bp, which encodes a 206-amino acid protein. A 6614-bp full-length IGF2a DNA molecule, including the 5'-flanking region, was isolated. Genomic DNA structure analysis revealed that the IGF2a gene contains four exons and three introns. Bioinformatics analysis indicated that the proteins encoded by IGF2a genes in common carp have one signal peptide and one apparent transmembrane region. Bootstrapping was performed 1000 times to obtain support values for each branch. The common carp IGF2a were clustered in one group, while the outgroup (common carp IGF1) clustered in another group. We identified two new single nucleotide polymorphisms in intron 2 of the gene. One polymorphism, A/N, can be found only in the Huanghe carp. The other polymorphism, C/N, can be found in both male Huanghe carp × female Heilongjiang carp and male Huanghe carp × female Jian carp. The second polymorphism, C/N, is primarily transferred from the male and may be related to heterosis.