RESUMEN
Abnormal expression of microRNA-135a (miR-135a) is closely associated with oncogenesis. However, the relationship between serum miR-135a levels and the clinical parameters and prognosis of non-small cell lung cancer (NSCLC) remain unclear. The study aimed to investigate the clinical significance of serum miR-135a expression in patients with NSCLC. miR-135a expression was analyzed by real-time PCR and its correlation with NSCLC was determined by various statistical methods for 104 NSCLC patients and 40 healthy volunteers. The serum miR-135a level was significantly lower in NSCLC patients than in healthy control subjects (P < 0.01), and was closely related to distant metastasis (P < 0.015), lymphatic metastasis (P = 0.000), TNM (tumor node metastasis) stage (P = 0.001), and pathological stage (P = 0.021) of NSCLC. The five year overall survival was significantly lower in patients with low miR-135a expression than that in patients with high serum miR-135a levels (P = 0.010). Multivariate analysis showed that serum miR-135a level could be treated as an independent risk factor for NSCLC prognosis (P = 0.011). In conclusion, the serum miR-135a level was downregulated in NSCLC patients, and was associated with poor prognosis. Additionally, it can be used as a biomarker for NSCLC prognosis.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Neoplasias Pulmonares/sangre , MicroARNs/sangre , Adulto , Anciano , Anciano de 80 o más Años , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Estudios de Casos y Controles , Regulación hacia Abajo , Femenino , Humanos , Estimación de Kaplan-Meier , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Análisis Multivariante , PronósticoRESUMEN
The CMYA1 (cardiomyopathy-associated protein 1) is an actin-binding protein that plays a vital role in cardiac morphogenesis. CMYA1 is expressed specifically in the myocardial and skeletal muscle and is up-regulated in injured muscle. We therefore speculated that the bovine CMYA1 promoter might be muscle-specific. In this study, the promoter (+20/-1135) region of the bovine CMYA1 gene was cloned into a pEGFP-1 vector, and we found that the EGFP was observed only in C2C12 and myoblast cells. Thus, the CMYA1 promoter is muscle-specific. Thereafter, eight pGL3-basic vectors with various truncated CMYA1 promoter fragments were transfected into C2C12 cells, to identify the core promoter region using a Dual-Luciferase Reporter Assay System. The results showed that the promoter region from -457 to +20 bp was essential for CMYA1 to maintain the promoter activity, implying that this region may be the CMYA1 core promoter. We thus illustrate that the core promoter is muscle-specific. To evaluate the activity of the CMYA1 core promoter, the CMYA1 core and muscle creatine kinase (MCK) promoters were cloned into a pcDNA3.1 vector. The expression levels of their target genes were measured in C2C12 cells using real-time polymerase chain reaction. The CMYA1 promoter drove the expression of the target gene six times higher than did the MCK promoter. The results thus suggest that the CMYA1 promoter could be an effective muscle-specific promoter, which may be useful in further studies of cardiomyopathy treatment and transgenic animal research.
Asunto(s)
Proteínas de Unión al ADN/genética , Corazón/crecimiento & desarrollo , Morfogénesis/genética , Regiones Promotoras Genéticas , Animales , Cardiomiopatías/genética , Cardiomiopatías/patología , Bovinos , Línea Celular , Genes Reporteros , Vectores Genéticos , Humanos , Ratones , Activación Transcripcional/genética , Transfección/métodosRESUMEN
Adipocyte fatty acid-binding protein (A-FABP), the most abundant FABP in adipocytes, controls fatty acid uptake, transport, and metabolism in fat cells. We constructed a transgenic mice model that overexpressed the cattle A-FABP gene to investigate the relationship between A-FABP expression and intermuscular fat deposition. There was no significant difference in body weight and serum biochemical indexes between transgenic and wild-type mice. Further, there were no significant differences in intermuscular triglyceride content and A-FABP expression levels over three generations of transgenic mice. However, abdominal adipose rate, A-FABP protein content, and intermuscular triglyceride levels of transgenic mice were significantly higher than those of wild-type mice. In addition, triglycerides were remarkably higher in the skeletal muscle but lower in the myocardium of transgenic mice. Thus, overexpression of cattle A-FABP gene promoted fat deposition in the skeletal muscle of transgenic mice.