RESUMEN
The receptor activator of nuclear factor κB ligand (RANKL)/RANK pathway plays an important role in the prognosis of several solid tumor types, but its role in gastric cancer prognosis has been poorly characterized. A total of 116 gastric cancer patients who underwent surgical resection were enrolled in this study. Expressions of RANKL and RANK in gastric cancer tissues were detected using immunohistochemical staining. Thirty-eight patients (33%) showed a high level of RANKL expression and 61 patients (53%) showed a high level of RANK expression. There was a positive correlation between expressions of RANKL and RANK (P=0.014, r=0.221). A high level of RANKL expression indicated shorter overall survival (OS) (P=0.008), and was associated with a higher pathological tumor/lymph node/metastasis (pTNM) stage (P=0.035), while no significant correlation was detected between RANK expression and clinicopathological parameters. RANKL also predicted poor prognosis in patients with high RANK expression (P=0.008) and Bormann's type III/IV (P=0.002). Furthermore, RANKL expression correlated with pTNM stage according to high RANK expression (P=0.009), while no significance was found in patients with low RANK expression (P=1.000). Together, our results revealed that high expression of RANKL could predict worse outcomes in gastric cancer especially combined with RANK detection, and thereby this pathway could be a useful prognostic indicator of gastric cancer.
Asunto(s)
Adenocarcinoma/metabolismo , Proteínas de Neoplasias/metabolismo , Ligando RANK/metabolismo , Neoplasias Gástricas/metabolismo , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Adenocarcinoma/cirugía , China/epidemiología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Inmunohistoquímica , Masculino , Persona de Mediana Edad , Clasificación del Tumor , Estadificación de Neoplasias , Pronóstico , Estudios Retrospectivos , Estadísticas no Paramétricas , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Neoplasias Gástricas/cirugíaRESUMEN
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.
Asunto(s)
Humanos , Neoplasias del Colon/tratamiento farmacológico , Fosfohidrolasa PTEN/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Exosomas/efectos de los fármacos , Cetuximab/farmacología , Antineoplásicos Inmunológicos/farmacología , Sales de Tetrazolio , Factores de Tiempo , Western Blotting , Análisis de Varianza , Células CACO-2 , Línea Celular TumoralRESUMEN
The receptor activator of nuclear factor κB ligand (RANKL)/RANK pathway plays an important role in the prognosis of several solid tumor types, but its role in gastric cancer prognosis has been poorly characterized. A total of 116 gastric cancer patients who underwent surgical resection were enrolled in this study. Expressions of RANKL and RANK in gastric cancer tissues were detected using immunohistochemical staining. Thirty-eight patients (33%) showed a high level of RANKL expression and 61 patients (53%) showed a high level of RANK expression. There was a positive correlation between expressions of RANKL and RANK (P=0.014, r=0.221). A high level of RANKL expression indicated shorter overall survival (OS) (P=0.008), and was associated with a higher pathological tumor/lymph node/metastasis (pTNM) stage (P=0.035), while no significant correlation was detected between RANK expression and clinicopathological parameters. RANKL also predicted poor prognosis in patients with high RANK expression (P=0.008) and Bormann's type III/IV (P=0.002). Furthermore, RANKL expression correlated with pTNM stage according to high RANK expression (P=0.009), while no significance was found in patients with low RANK expression (P=1.000). Together, our results revealed that high expression of RANKL could predict worse outcomes in gastric cancer especially combined with RANK detection, and thereby this pathway could be a useful prognostic indicator of gastric cancer.
Asunto(s)
Humanos , Masculino , Femenino , Persona de Mediana Edad , Neoplasias Gástricas/metabolismo , Adenocarcinoma/metabolismo , Ligando RANK/metabolismo , Proteínas de Neoplasias/metabolismo , Pronóstico , Neoplasias Gástricas/cirugía , Neoplasias Gástricas/mortalidad , Neoplasias Gástricas/patología , Inmunohistoquímica , Adenocarcinoma/cirugía , Adenocarcinoma/mortalidad , Adenocarcinoma/patología , Regulación Neoplásica de la Expresión Génica , China/epidemiología , Estudios Retrospectivos , Estadísticas no Paramétricas , Clasificación del Tumor , Estadificación de NeoplasiasRESUMEN
Cetuximab is widely used in patients with metastatic colon cancer expressing wildtype KRAS. However, acquired drug resistance limits its clinical efficacy. Exosomes are nanosized vesicles secreted by various cell types. Tumor cell-derived exosomes participate in many biological processes, including tumor invasion, metastasis, and drug resistance. In this study, exosomes derived from cetuximab-resistant RKO colon cancer cells induced cetuximab resistance in cetuximab-sensitive Caco-2 cells. Meanwhile, exosomes from RKO and Caco-2 cells showed different levels of phosphatase and tensin homolog (PTEN) and phosphor-Akt. Furthermore, reduced PTEN and increased phosphorylated Akt levels were found in Caco-2 cells after exposure to RKO cell-derived exosomes. Moreover, an Akt inhibitor prevented RKO cell-derived exosome-induced drug resistance in Caco-2 cells. These findings provide novel evidence that exosomes derived from cetuximab-resistant cells could induce cetuximab resistance in cetuximab-sensitive cells, by downregulating PTEN and increasing phosphorylated Akt levels.
Asunto(s)
Antineoplásicos Inmunológicos/farmacología , Cetuximab/farmacología , Neoplasias del Colon/tratamiento farmacológico , Exosomas/efectos de los fármacos , Fosfohidrolasa PTEN/efectos de los fármacos , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Análisis de Varianza , Western Blotting , Células CACO-2 , Línea Celular Tumoral , Supervivencia Celular/efectos de los fármacos , Neoplasias del Colon/metabolismo , Resistencia a Medicamentos , Exosomas/metabolismo , Formazáns , Humanos , Fosfohidrolasa PTEN/análisis , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/análisis , Proteínas Proto-Oncogénicas c-akt/metabolismo , Sales de Tetrazolio , Factores de TiempoRESUMEN
Twenty-four polymorphic microsatellite loci were isolated and characterized for Liza affinis using a (GT)13-enriched genomic library. The number of alleles per locus ranged from 3 to 9, with a mean number of 6.250. The observed and expected heterozygosities ranged from 0.417 to 1.000 and from 0.550 to 0.861, with an average of 0.859 and 0.779, respectively. Deviation from Hardy-Weinberg proportions was detected at three loci. Evidence of null alleles was found at two loci. These markers will be useful in further studies investigating the genetic variation and population structure of this species, and may provide insights into the maintenance and efficient management of eastern keelback mullet resources.
Asunto(s)
Repeticiones de Microsatélite , Smegmamorpha/genética , Animales , China , Polimorfismo GenéticoRESUMEN
Sillago sinica is a newly identified species belonging to Sillaginidae, Perciforms, and was found along the coast of China in 2011. In the present study, 81 microsatellite loci were isolated from an enriched genomic library, and 24 positive clones containing microsatellite repeats had adequate flanking sequences for the development of PCR primers. Sixteen of these primers were monomorphic or would not amplify. Eight were polymorphic in an examined population with the number of alleles per locus ranging from 2 to 14. The number of observed and expected heterozygosities per locus varied from 0.125 to 0.958 and from 0.120 to 0.904, respectively. The polymorphism information content ranged from 0.110 to 0.721. All loci conformed to Hardy-Weinberg equilibrium (P > 0.05) after Bonferroni correction. There was no significant linkage disequilibrium between the eight polymorphic loci. These results suggest that these markers may be very useful for the characterization of natural populations of this species.
Asunto(s)
Repeticiones de Microsatélite , Perciformes/genética , Alelos , Animales , Genoma , Heterocigoto , Desequilibrio de Ligamiento , Polimorfismo GenéticoRESUMEN
Growth and meat quality traits play important roles in the evaluation of cattle productivity and are influenced by genetic and environmental factors. CRTC2 is a recently discovered gene related to obesity that may influence fat deposition. The aim of the current study was to detect polymorphisms of bovine CRTC2 and explore their relationships to growth and meat quality in Qinchuan cattle. Three single nucleotide polymorphisms (SNPs); g.3001 C>T; g.3034 G>A; and g.3467 T>C, were identified from sequencing results of 422 Qinchuan cattle. The genotypic distributions of both g.3034 G>A and g.3467 T>C mutations were in agreement with Hardy-Weinberg equilibrium, (P < 0.05), while the T3001C mutation was not (P > 0.05), based on χ(2) test analysis. The SNPs g.3001 C>T and g.3034 G>A are missense mutations (Ser/Phe and Ser/Thr respectively). Additionally, SNPs g.3034 G>A and g.3467 T>C showed a medium polymorphism level (0.25 < PIC< 0.50), whereas g.3001 C>T showed a low polymorphism level (PIC < 0.25). These three SNPs were significantly associated with several growth and meat quality traits in the Qinchuan cattle population (P < 0.05 or P < 0.01). Collectively, these results demonstrate that CRTC2 is involved in the regulation of cattle growth and meat quality, and suggest that CRTC2 is a potential candidate gene for marker-assisted selection in future breeding development programs for Qinchuan cattle.
Asunto(s)
Bovinos/genética , Carne/normas , Polimorfismo de Nucleótido Simple/genética , Factores de Transcripción/genética , Alelos , Animales , Frecuencia de los Genes/genética , Estudios de Asociación Genética , Genotipo , Técnicas de Genotipaje , Análisis de Secuencia de ADNRESUMEN
Previous studies have shown that the signal transducer and activator of transcription 3 gene (STAT3) is involved in lipid storage and energy metabolism, suggesting that STAT3 is a potential candidate gene that affects body measurement and carcass quality traits in animals. Therefore, the aim of this study was to identify polymorphisms in bovine STAT3 and to analyze their possible associations with body measurement and carcass quality traits in 493 individuals of 2 native Chinese cattle breeds: Qinchuan (N = 371) and Jiaxian cattle (N = 122). DNA sequencing and polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were employed to detect STAT3 single nucleotide polymorphisms (SNPs). We found 5 SNPs: 1 in an exon (g.65812G>A: exon 16) and 4 in introns (g.43591G>A: 13 intron, g.67492T>G: 19 intron, g.67519T>C: 19 intron, and g.68964G>A: 20 intron). Both g.65812G>A and g.68964G>A were not in Hardy- Weinberg equilibrium (HWE), whereas individual frequencies of each genotype were consistent with HWE for other SNPs in Qinchuan cattle populations. For the Jiaxian cattle, the genotype distributions of the 4 mutations were in HWE except for g.67519T>C. The results indicate that these SNPs have a significant association with some body measurements and carcass quality traits (P < 0.05 or P < 0.01). Therefore, STAT3 might have potential effects on production traits in beef cattle populations and could be used for marker-assisted selection.
Asunto(s)
Carne/normas , Factor de Transcripción STAT3/genética , Animales , Tamaño Corporal/genética , Cruzamiento , Bovinos/genética , Bovinos/crecimiento & desarrollo , Calidad de los Alimentos , Frecuencia de los Genes , Estudios de Asociación Genética , Marcadores Genéticos , Polimorfismo de Nucleótido Simple , Selección Genética , Análisis de Secuencia de ADNRESUMEN
MicroRNAs (miRNAs) play critical roles in post-transcriptional gene regulation and act as important endogenous regulators to various stressors. Ultraviolet-B (UV-B) radiation is a major factor influencing crop growth and development. In this study, we isolated a novel wheat miRNA, named Tae-miR6000, and confirmed its expression diversity after UV-B treatments. Additionally, using the Northern blotting technique, we found that six miRNAs were highly responsive to UV-B stress in wheat. Of these six miRNAs, miR159, miR167a, and miR171 were significantly upregulated, and the remaining three miRNAs were downregulated, at different time points after UV-B treatment. This result indicates that miRNAs may be involved in the regulation of targets after induction by UV-B stress. Furthermore, promoter analysis of the UV-B-responsive miRNA genes revealed some light-relevant cis-elements, such as the I-box and G-box. Taken together, the results of this study suggest that wheat miRNAs play important roles in the response to UV-B stress.