RESUMEN
CircRNA-0068481 and several miRNAs are important in the pathogenesis of right ventricular hypertrophy (VH), while the inhibition of eye absent transcriptional coactivator and phosphatase 3 (EYA3) was proved to reverse vascular remodelling in rats. In this study, we tried to study the diagnostic value and mechanistic role of circRNA_0068481 in the diagnosis of RVH in PAH patients. qPCR was done to measure circRNA-0068481, miR-646, miR-750, miR-885 and EYA3 mRNA expression. Luciferase assay was done to explore the regulatory relationship between circRNA-0068481/EYA3 and the miRNAs. Western blot was done to measure EYA3 expression in AC16 cells. The expression of circRNA-0068481, miR-646 and miR-570 showed a considerable capability to diagnose RVH in PAH patients. The luciferase activity of circRNA-0068481 was remarkably suppressed by miR-646, miR-570 or miR-885. The luciferase signal of EYA3 was also inhibited by miR-646, miR-570 and miR-885. Up-regulation of circRNA-0068481 expression in AC16 significantly decreased miR-646, miR-570 and miR-885 expression, and up-regulated EYA3 expression, whereas circRNA-0068481 down-regulation significantly increased miR-646, miR-570 and miR-885 expression, and repressed EYA3 expression. CircRNA_0068481 sponged several miRNAs including miR-646, miR-570 and miR-885. These miRNAs were all found to target the expression of EYA3 mRNA, which is involved in the onset of right ventricular hypertrophy. Therefore, it can be concluded that the up-regulation of circRNA_0068481 can predict the diagnosis of right ventricular hypertrophy in pulmonary arterial hypertension patients.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Regulación de la Expresión Génica , Hipertrofia Ventricular Derecha/patología , MicroARNs/genética , Proteínas Tirosina Fosfatasas/metabolismo , ARN Circular/genética , Apoptosis , Biomarcadores/metabolismo , Proliferación Celular , Células Cultivadas , Proteínas de Unión al ADN/genética , Femenino , Humanos , Hipertrofia Ventricular Derecha/genética , Hipertrofia Ventricular Derecha/metabolismo , Masculino , Persona de Mediana Edad , Pronóstico , Proteínas Tirosina Fosfatasas/genéticaRESUMEN
Increasing data shows miR-29a is a key regulator of oncogenic processes. It is significantly down-regulated in some kind of human tumors and possibly functionally linked to cellular proliferation, survival and migration. However, the mechanism remains unclear. In this study, we report miR-29a is significantly under-expressed in gastric cancer compared to the healthy donor. The microvessel density is negatively related to miR-29a expression in gastric cancer tissues. The ectopic expression of miR-29a significantly inhibits proliferation and invasion of gastric cancer cells. Furthermore, western blot combined with the luciferase reporter assays demonstrate that vascular endothelial growth factor A (VEGF-A) is direct target of miR-29a. This is the first time miR-29a was found to suppress the tumor microvessel density in gastric cancer by targeting VEGF-A. Taken together, these results suggest that miR-29a is a tumor suppressor in gastric cancer. Restoration of miR-29a in gastric cancer may be a promising therapeutic approach.