RESUMEN
Presbycusis affects approximately one-third of people over the age of 65 and is a worldwide health problem. In the current study, whether the methylation level of solute carrier family 26 member 4 (SLC26A4) predicted an increased risk of presbycusis was investigated. Peripheral blood samples from 102 patients with presbycusis and 104 controls were collected, and the methylation of the CpG sites of SLC26A4 was measured by applying pyrosequencing technology combined with sodium bisulfate DNA conversion chemistry. Within the SLC26A4 promoter region, one CpG site (CpG3) exhibited a significantly (P<0.0001) greater methylation level in the patients with presbycusis (26.5±5.56%) compared with the controls (23.8±3.85%). Significantly different CpG3 methylation levels were observed between the patients with presbycusis and the controls among the male participants (P=0.0004). In addition, a significant decrease in the transcriptional level of SLC26A4 in peripheral blood was observed in the patients with presbycusis compared with the controls. Furthermore, analyses of the receiver operating characteristic (ROC) curves indicated that CpG3 methylation at the SLC26A4 promoter predicted the risk of presbycusis in the male participants (AUC=0.684, 95% CI=0.5840.784, P=0.001). The results demonstrated the significance of the CpG site methylation level of SLC26A4, and thus provides a potential marker for the diagnosis of presbycusis.
Asunto(s)
Metilación de ADN , Estudios de Asociación Genética , Predisposición Genética a la Enfermedad , Proteínas de Transporte de Membrana/genética , Presbiacusia/genética , Regiones Promotoras Genéticas , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Islas de CpG , Epigénesis Genética , Regulación de la Expresión Génica , Humanos , Masculino , Persona de Mediana Edad , Curva ROC , Factores Sexuales , Transportadores de Sulfato , Transcripción GenéticaRESUMEN
Long non-coding RNAs (lncRNAs) play an important role in cancer occurrence and development. We previously demonstrated that lncRNA gastric cancer-associated transcript 3 (GACAT3) was positively correlated with TNM stages, tumor size, and distant metastasis of patients with gastric cancer. However, the role of GACAT3 in gastric cancer remains unclear. In this study, to investigate its function, we synthesized small interference RNAs (siRNAs) against GACTA3 and developed a GACAT3 overexpression vector (pcDNA3-GACAT3), respectively. The siRNA-mediated knockdown of GACAT3 significantly decreased cell proliferation of the gastric cancer HGC-27 cells, in which GACAT3 is overexpressed. Furthermore, GACAT3 overexpression in gastric cancer SGC-7901 cells promoted cell growth. Moreover, GACAT3 expression in HGC-27 cells was greatly upregulated by IL-6 treatment in a concentration-dependent manner. In contrast, siRNA-mediated knockdown of STAT3 decreased GACAT3 expression even in the presence of IL-6. These results demonstrated that as a downstream target of the IL6/STAT3 signaling, lncRNA GACAT3 promotes gastric cancer cell growth suggesting that GACAT3 is an inflammatory response gene and may be served as a valuable potential target for the treatment of gastric cancer.
Asunto(s)
Transformación Celular Neoplásica/genética , Interleucina-6/metabolismo , ARN Largo no Codificante/genética , Factor de Transcripción STAT3/genética , Factor de Transcripción STAT3/metabolismo , Neoplasias Gástricas/genética , Biomarcadores de Tumor/genética , Línea Celular Tumoral , Proliferación Celular/genética , Humanos , Interferencia de ARN , ARN Interferente Pequeño , Transducción de Señal , Neoplasias Gástricas/patologíaRESUMEN
Adipogenesis is orchestrated by a highly ordered network of transcription factors including peroxisome-proliferator activated receptor-gamma (PPARγ) and CCAAT-enhancer binding protein (C/EBP) family proteins. High mobility group protein AT-hook 2 (HMGA2), an architectural transcription factor, has been reported to play an essential role in preadipocyte proliferation, and its overexpression has been implicated in obesity in mice and humans. However, the direct role of HMGA2 in regulating the gene expression program during adipogenesis is not known. Here, we demonstrate that HMGA2 is required for C/EBPß-mediated expression of PPARγ, and thus promotes adipogenic differentiation. We observed a transient but marked increase of Hmga2 transcript at an early phase of differentiation of mouse 3T3-L1 preadipocytes. Importantly, Hmga2 knockdown greatly impaired adipocyte formation, while its overexpression promoted the formation of mature adipocytes. We found that HMGA2 colocalized with C/EBPß in the nucleus and was required for the recruitment of C/EBPß to its binding element at the Pparγ2 promoter. Accordingly, HMGA2 and C/EBPß cooperatively enhanced the Pparγ2 promoter activity. Our results indicate that HMGA2 is an essential constituent of the adipogenic transcription factor network, and thus its function may be affected during the course of obesity.
