RESUMEN
Endometrial cancer (EC) is generally considered as a disease that affects older women. We attempt to explore the role of actinlike protein 8 (ACTL8) in EC and how it achieves its function. Based on the data from The Cancer Genome Atlas (TCGA), we found that ACTL8 expression was up-regulated in EC tissues and correlated with shorter overall survival of EC patients. ACTL8 expression was significantly associated with age, clinical-stage, or grade. Cox proportional hazards model analysis revealed that ACTL8 expression, grade, and clinical-stage were promising independent prognostic factors of EC. Knockdown of ACTL8 repressed the proliferative, migrating and invading capabilities of human EC cell lines KLE and Ishikawa. Silencing ACTL8 up-regulated the negative cell cycle regulator p21 and epithelial marker E-cadherin, and down-regulated the positive cell cycle regulator Cyclin A, mesenchymal markers MMP-9 and N-cadherin in KLE cells. Collectively, these outcomes illustrated that ACTL8 might act as a tumor facilitator during EC progression.
Asunto(s)
Actinas/metabolismo , Biomarcadores de Tumor/metabolismo , Proteínas del Citoesqueleto/metabolismo , Progresión de la Enfermedad , Neoplasias Endometriales/metabolismo , Actinas/genética , Antígenos CD/metabolismo , Biomarcadores de Tumor/genética , Cadherinas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Supervivencia Celular/genética , Ciclina A/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Proteínas del Citoesqueleto/genética , Regulación hacia Abajo/genética , Neoplasias Endometriales/patología , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Metaloproteinasa 9 de la Matriz/metabolismo , Persona de Mediana Edad , Pronóstico , Transducción de Señal/genética , Transfección , Regulación hacia Arriba/genéticaRESUMEN
OBJECTIVE: To analyze the status of DACH1 gene promoter methylation and explore its association with the expression of DACH1 gene promoter methylation and clinical significance of endometrium carcinoma (EC). METHODS: From February 2004 to August 2008, a total of 80 EC tissue samples with comprehensive surgical pathology staging were collected and used for this study. Twenty normal endometrium tissues in 2008 were abstained from the fractional curettage because of dysfunctional uterine bleeding as control. All samples were confirmed pathologically. Methylation specific PCR (MSP) was performed to detect the promoter methylation of DACH1 gene, and analyze its influence on the expression of DACH1 and the relationship between DACH1 promoter methylation and clinicopathological factors in EC. DACH1 protein expression was detected by western blot. Chi-square test and Pearson test were used for statistical analysis. RESULTS: The rate of promoter methylation of DACH1 gene in the EC tissues was significantly higher than that in the normal endometrium issues (30% vs. 5%, P < 0.05). There was an association between the expression of DACH1 and DACH1 gene promoter methylation (r = -0.30, P < 0.01). There was statistical difference between the methylation of DACH1 and the pathological grade (P < 0.05) or histological type (P < 0.05). But DACH1 gene methylation was not related with the age, stage, myometrial invasion depth and lymphnode metastasis (P > 0.05). CONCLUSIONS: DACH1 gene promoter methylaion could lead to a decrease or absence in the DACH1 expression in EC. The promoter methylation of DACH1 gene may induce the inhibition of DACH1 expression, which might be one of the mechanisms of DACH1 gene inactivation in human EC.