RESUMO
We conducted a case-control study to investigate the role of interleukin-17A (IL-17A) rs2275913 G > A and IL-17F rs763780 T > C polymorphisms in the development of gastric cancer. A hospital-based case-control design was performed, and 153 patients and 207 control subjects were consecutively selected from the Third Affiliated Hospital between May 2013 and December 2014. Polymerase chain reaction-restriction fragment length polymorphism was used to genotype for IL-17A rs2275913 G > A and IL-17F rs763780 T > C. The genotypes of IL-17A rs2275913 G > A and IL-17F rs763780 T > C did not deviate from Hardy-Weinberg equilibrium (P values were 0.44 and 0.11, respectively). By unconditional logistic regression analysis, we observed that the GG genotype of rs2275913 was associated with an increased risk of gastric cancer compared to the AA genotype [odds ratio (OR) = 2.66; 95% confidence interval (CI) = 1.26-5.66]. The AG + GG genotype of rs2275913 increased the susceptibility to gastric cancer compared to the AA genotype, and the adjusted OR (95%CI) was 2.66 (1.26-5.66). Moreover, the GG genotype of rs2275913 was correlated with an elevated risk of gastric cancer when compared with the AA + AG genotype (OR = 2.15; 95%CI = 1.08-4.34). In conclusion, we found that the IL-17A rs2275913 G > A gene polymorphism was significantly associated with an increased risk of gastric cancer in co-dominant, dominant, and recessive models.
Assuntos
Povo Asiático/genética , Predisposição Genética para Doença , Interleucina-17/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Gástricas/genética , Estudos de Casos e Controles , China , Estudos de Associação Genética , Humanos , RiscoRESUMO
The NF-kB (nuclear factor kB) pathway is involved in the proliferation of many cell types. To explore the mechanism of the NF-kB signaling pathway underlying the oval cell proliferation during rat liver regeneration, the Rat Genome 230 2.0 Array was used to detect expression changes of NF-kB signaling pathway-related genes in oval cells. The results revealed that the expression levels of many genes in the NF-kB pathway were significantly changed. This included 48 known genes and 16 homologous genes, as well as 370 genes and 85 homologous genes related to cell proliferation. To further understand the biological significance of these changes, an expression profile function was used to analyze the potential biological processes. The results showed that the NF-kB pathway promoted oval cell proliferation mainly through three signaling branches; the tumor necrosis factor alpha branch (TNF-a pathway), the growth factor branch, and the chemokine branch. An integrated statistics method was used to define the key genes in the NF-kB pathway. Seven genes were identified to play vital roles in the NF-kB pathway. To confirm these results, the protein content, including two key genes (TNF and FGF11) and two non-key genes (CCL2 and TNFRSF12A), were analyzed using two-dimensional gel electrophoresis and MALDI-TOF/TOF mass spectrometry. The results were generally consistent with those of the array data. To conclude, three branches and seven key genes were involved in the NF-kB signaling pathway that regulates oval cell proliferation during rat liver regeneration.
Assuntos
Proliferação de Células , Regeneração Hepática , Fígado/metabolismo , NF-kappa B/metabolismo , Transdução de Sinais , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Fatores de Crescimento de Fibroblastos/genética , Fatores de Crescimento de Fibroblastos/metabolismo , Fígado/citologia , Fígado/fisiologia , NF-kappa B/genética , Ratos , Receptores do Fator de Necrose Tumoral/genética , Receptores do Fator de Necrose Tumoral/metabolismo , Receptor de TWEAK , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Previous studies have demonstrated that the nuclear factor κB (NF-κB) pathway is involved in promoting cell proliferation. To further explore the regulatory branches and their sequence in the NF-κB pathway in the promotion of hepatocyte proliferation at the transcriptional level during rat liver regeneration, Rat Genome 230 2.0 array was used to detect the expression changes of the isolated hepatocytes. We found that many genes involved in the NF-κB pathway (including 73 known genes and 19 homologous genes) and cell proliferation (including 484 genes and 104 homologous genes) were associated with liver regeneration. Expression profile function (Ep) was used to analyze the biological processes. It was revealed that the NF-κB pathway promoted hepatocyte proliferation through three branches. Several methods of integrated statistics were applied to extract and screen key genes in liver regeneration, and it indicated that eight genes may play a vital role in rat liver regeneration. To confirm the above predicted results, Ccnd1, Jun and Myc were analyzed using qRT-PCR, and the results were generally consistent with that of microarray data. It is concluded that 3 branches and 8 key genes involved in the NF-κB pathway regulate hepatocyte proliferation during rat liver regeneration.
Assuntos
Hepatócitos/citologia , Hepatócitos/metabolismo , Regeneração Hepática/genética , NF-kappa B/metabolismo , Transdução de Sinais/genética , Animais , Proliferação de Células , Regulação da Expressão Gênica , Modelos Biológicos , Análise de Sequência com Séries de Oligonucleotídeos , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo RealRESUMO
We examined the gene expression profiles of the 5-hydroxytryptamine signaling pathway in the regenerating liver and 8 types of liver cells during rat liver regeneration, and explored expression differences in 5-hydroxytryptamine signaling pathway genes at the level of tissues and cells, as well as the role of the pathway on liver regeneration. Eight types of rat regenerating liver cells were isolated using Percoll density-gradient centrifugation and immunomagnetic bead methods. Rat Genome 230 2.0 Array was used to detect expression changes in 5-hydroxytryptamine signaling pathway genes. The results showed that 26, 47, 8, 21, 16, 19, 22, 27, and 20 genes changed significantly in hepatocytes, biliary epithelial cells, hepatic stellate cells, oval cells, sinusoidal endothelial cells, Kupffer cells, pit cells, dendritic cells, and the regenerating liver, respectively. Synthetic effects of 5-hydroxytryptamine signaling pathway genes in 8 types of liver cells showed that 26 genes were expressed significantly; the expression trends of 10 genes were the same in the regenerating liver, while others were different. Based on the gene expression profiles of the 8 types of liver cells, 5-hydroxytryptamine promoted hepatocyte proliferation through the RAS and STAT3 signaling pathways, proliferation and differentiation of sinusoidal endothelial cells through the STAT3 signaling pathway, and proliferation and apoptosis of pit cells through the AKT3 signaling pathway. There were large differences in genes involved in 5-hydroxytryptamine signaling at the tissue and cellular levels; thus, liver regeneration should be studied in-depth at the cellular level to reveal the molecular mechanism of liver regeneration.