RESUMEN

BACKGROUND: The mortality rate for liver cancer is high worldwide. The etiology of liver cancer has altered with the high incidence rate of non-alcoholic fatty liver disease (NAFLD) although effective vaccination strategies have been developed. Therefore, it is important to discover new biomarkers for diagnosis and prognosis. Aquaporin 9 (AQP9) has been reported in some cancers, especially in liver cancer, although its role in this malignancy remains to be clarified. In this study, we conducted a bioinformatics analysis to clarify the function of AQP9 in liver cancer. METHODS: Immunohistochemistry, real-time qPCR, western blot analysis were applied to detect AQP9 expression in tissue samples or cells. Online databases were used to analyze the correlation of AQP9 expression and clinical factors. LinkedOmics and gene set enrichment analysis (GSEA) were used to analyze the functional network of AQP9 in hepatocellular carcinoma (HCC). Four authoritative databases were used to predict the candidate microRNAs that bind to AQP9. Finally, we used the Tumor Immune Estimation Resource (TIMER) to assess the correlation of AQP9 and immune cell infiltration in HCC. RESULTS: All analysis were revealed AQP9 is significantly decreased in HCC tissues and cells. AQP9 was negatively correlated with different tumor stage, grade, and weight, as well as lymph node metastasis, sex, and histological subtypes. AQP9 can be used to predict the prognosis of HCC patients. GSEA revealed that AQP9 was significantly involved in most significant hallmark pathways. LinkedOmics was used to analyze the relationship of AQP9 with Gene Ontology and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Mechanistically, mir-23a-3p and mir-330-3p may downregulate AQP9 expression in HCC. AQP9 was found to be specifically correlated with immune cell infiltration and play a major role in the liver cancer microenvironment. CONCLUSIONS: In this study, we found that AQP9 was significantly decreased in HCC, with low AQP9 levels indicating a poor outcome. GSEA analysis and LinkedOmics revealed that AQP9 was significantly involved in the most significant hallmarks pathways. Mir-23a-3p and mir-330-3p may inhibit AQP9 expression in HCC. Our results also suggest that AQP9 is important in tumor immunity in the liver cancer.

RESUMEN

Aquaporin 9 plays critical roles in aspects of energy homeostasis, metabolism, gluconeogenesis, fat synthesis and even the individual growth and development. So the Aquaporin 9 (AQP9) gene is a potential candidate gene for bovine growth traits. In this study, we detected the polymorphism of the bovine AQP9 gene including all exons by PCR-SSCP and DNA sequencing methods with six pairs of PCR primers in 555 individuals from three cattle breeds. Three novel SNPs (NC_007308:g.47575 C > T, 47615 C > T, 47690A > G) were detected using P6 primer. The linkage disequilibrium analysis indicated that the three SNPs were completely linked (r2 = 1), which constructed three genotypes (AA, AB, BB). The genotype AB was dominant in all three breeds. The frequencies of haplotype A and haplotype B were almost equivalent between each other. The individuals with genotype AB were significantly higher than those individuals with genotype BB in body weight (p < 0.01), chest circumference (p < 0.05) and rump length (p < 0.05). Moreover, individuals with genotype AA were significantly higher than those of individuals with genotype BB in body height (p < 0.01). These results suggested that the novel SNPs could be a perfect molecular marker for marker-assisted selection (MAS) breeding.

Asunto(s)

Acuaporinas/metabolismo , Bovinos/crecimiento & desarrollo , Bovinos/genética , Haplotipos/genética , Secuencia de Aminoácidos , Animales , Acuaporinas/genética , Secuencia de Bases , ADN/genética , Genotipo , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple

RESUMEN

10-Hydroxy-trans-2-decenoic acid (10H2DA) is a unique lipid component of royal jelly produced by worker honeybees that exerts insulin-like effects. We herein investigated the effects of 10H2DA on the gene expression of aquaporin 9 (AQP9), which functions as a glycerol transporter in the liver, to clarify whether 10H2DA modulates energy metabolism. 10H2DA suppressed AQP9 gene expression in HepG2 cells by promoting the phosphorylation of Akt and AMP-activated protein kinase (AMPK). This suppression was partially recovered by the treatment of cells with inhibitors for Akt and AMPK. Based on the result showing that leptomycin B partially recovered the suppression of AQP9 gene expression, 10H2DA inhibited the expression of Foxa2, a transcription factor for the AQP9 gene, and also induced its nuclear exclusion. Although 10H2DA up-regulated phosphoenolpyruvate carboxykinase and glucose-6-phosphatase gene expression, this was suppressed through the modulation of Foxa2 by insulin. These results suggest that 10H2DA suppresses AQP9 gene expression through the phosphorylation of Akt and AMPK and down-regulation of Foxa2 expression.