RESUMEN
Hepatocellular carcinoma (HCC) is one of the most common cancers and a leading cause of cancer-related deaths worldwide. Early diagnosis of HCC remains a great challenge in clinic. Novel and effective biomarkers are in urgent need in early diagnosis of HCC.Serum levels of neurotrophin-receptor-interacting melanoma antigen-encoding gene homolog (NRAGE) were measured for 107 patients with HCC, 98 patients with benign liver diseases, and 89 healthy controls using quantitative real-time polymerase chain reaction. Receiver operating characteristic curve was applied to evaluate the diagnostic capacity of serum NRAGE in HCC.NRAGE expression was significantly higher in patients with HCC than in controls (all, Pâ<â.05). Moreover, its expression was tightly correlated with TNM stage (Pâ=â.004). NRAGE could distinguish patients with HCC from healthy controls with the area under the curve (AUC) of 0.874, yielding a sensitivity of 81.3% and a specificity of 78.7%. Additionally, in differentiation between benign liver diseases and HCC, the AUC value of NRAGE was 0.726, with a sensitivity of 63.6% and a specificity of 73.5%. Meanwhile, alpha-fetoprotein also could distinguish patients with HCC from benign liver disease cases, with an AUC of 0.677, a sensitivity of 64.4%, and a specificity of 60.2%.NRAGE could be a potential biomarker for HCC early diagnosis.
Asunto(s)
Antígenos de Neoplasias/sangre , Biomarcadores de Tumor/sangre , Carcinoma Hepatocelular/sangre , Neoplasias Hepáticas/sangre , Proteínas de Neoplasias/sangre , Adulto , Anciano , Área Bajo la Curva , Biomarcadores de Tumor/genética , Carcinoma Hepatocelular/genética , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Hepáticas/genética , Masculino , Persona de Mediana Edad , Reacción en Cadena en Tiempo Real de la Polimerasa , Sensibilidad y Especificidad , Regulación hacia Arriba , alfa-Fetoproteínas/análisisRESUMEN
microRNAs (miRNAs) play important roles in the pathogenesis of atherosclerosis. A previous study has reported that miR-497 is elevated in advanced atherosclerotic lesions in an apoE-deficient (apoE-/-) mouse model. The purpose of this study is to test whether miR-497 can modulate macrophage foam cell formation, an initiating event in atherosclerosis. We found that miR-497 was upregulated in THP-1 macrophages after treatment with oxidized low-density lipoprotein (oxLDL). Enforced expression of miR-497 promoted lipid accumulation and decreased cholesterol efflux in oxLDL-exposed THP-1 macrophages. In contrast, downregulation of miR-497 suppressed oxLDL-induced lipid accumulation in THP-1 macrophages. Apelin was identified to be a downstream target of miR-497. Overexpression of miR-497 significantly reduced the expression of apelin in THP-1 macrophages. Interestingly, delivery of a miR-497-resistant variant of apelin significantly inhibited lipid accumulation and enhanced cholesterol efflux in miR-497-overexpressing THP-1 macrophages in response to oxLDL. In addition, miR-497 expression was increased and negatively correlated with apelin protein expression in human atherosclerotic lesions. In conclusion, miR-497 contributes to oxLDL-induced lipid deposition in macrophages largely via targeting of apelin and thus represents a potential therapeutic target for atherosclerosis.
Asunto(s)
Apelina/antagonistas & inhibidores , Lipoproteínas LDL/fisiología , Macrófagos/metabolismo , MicroARNs/metabolismo , Transportadoras de Casetes de Unión a ATP/genética , Transportadoras de Casetes de Unión a ATP/metabolismo , Apelina/biosíntesis , Apelina/genética , Apelina/metabolismo , Apolipoproteínas E/genética , Aterosclerosis/genética , Aterosclerosis/metabolismo , Colesterol/metabolismo , Células Espumosas/citología , Células Espumosas/metabolismo , Humanos , Metabolismo de los Lípidos/genética , Lipoproteínas LDL/genética , Lipoproteínas LDL/metabolismo , Lipoproteínas LDL/farmacología , Macrófagos/citología , MicroARNs/genética , Células THP-1RESUMEN
Natural phytochemicals are attracting increasing interest as anticancer agents. The aim of this study is to evaluate the therapeutic potential of geraniin, a major ellagitannin extracted from Geranium sibiricum L., in human glioma. Human U87 and LN229 glioma cells were treated with different concentrations of geraniin, and cell viability, apoptosis, and gene expression were assessed. The involvement of STAT3 signaling in the action of geraniin was examined. We found that geraniin treatment for 48 h significantly (P < 0.05) impaired the phosphorylation of STAT3 and reduced the expression of downstream target genes Bcl-xL, Mcl-1, Bcl-2, and cyclin D1. Exposure to geraniin led to a concentration-dependent decline in cell viability and increase in apoptosis in glioma cells, but had no significant impact on the viability of normal human astrocytes. Measurement of caspase-3 activity showed that geraniin-treated U87 and LN229 cells showed a 1.8-2.5-fold higher caspase-3 activity than control cells. Overexpression of constitutively active STAT3 significantly (P < 0.05) reversed geraniin-mediated growth suppression and apoptosis, which was accompanied by restoration of Bcl-xL, Mcl-1, Bcl-2, and cyclin D1 expression. In an xenograft tumor mouse model, geraniin treatment significantly retarded tumor growth and induced apoptosis. Western blot analysis confirmed the suppression of STAT3 phosphorylation in glioma xenograft tumors by geraniin. Taken together, these data suggest that geraniin exerts growth-suppressive and pro-apoptotic effects on glioma cells via inhibition of STAT3 signaling and may have therapeutic benefits in malignant gliomas.