RESUMEN
Long noncoding RNA (lncRNA) dysregulation is known to be taking part in majority of cancers, including osteosarcoma. In one of our previous studies, we showed that lncRNA MEG3 is being regulated by microRNA-664a (miR-664a) suppresses the migratory potential of osteosarcoma cells (U-2OS). We now report a novel lncRNA, namely, ERICD, which is linked to the transcription factor AT-rich interaction domain 3A (ARID3A) in U-2OS cells. We show that ARID3A binds to ERICD and indirectly interacts with each other via the E2F transcription factor 1 (E2F1). Furthermore, small interfering RNA (siRNA)-mediated knockdown of ERICD inhibited cell migration, formation of colonies, and proliferation in U-2OS cells. Overexpression of ARID3A inhibited cell migration, colony formation, and proliferation, whereas siRNA-mediated knockdown of ARID3A promoted cell migration, colony formation, and proliferation. Our findings indicate that ARID3A and lncRNA ERICD have plausible tumor suppressive and oncogenic functions, respectively, in osteosarcoma. Our data demonstrate the converse interaction between ARID3A and lncRNA ERICD that target DNA-binding proteins and dysregulation of their expression through E2F1 augments osteosarcoma progression. The cell rescue experiment also indicated E2F1 to be involved in the regulation of ARID3A and ERICD.
Asunto(s)
Proteínas de Unión al ADN/metabolismo , Osteosarcoma/genética , ARN Largo no Codificante/genética , Factores de Transcripción/metabolismo , Apoptosis/genética , Neoplasias Óseas/patología , Línea Celular Tumoral , Movimiento Celular/genética , Proliferación Celular/genética , Proteínas de Unión al ADN/genética , Factor de Transcripción E2F1/genética , Factor de Transcripción E2F1/metabolismo , Regulación Neoplásica de la Expresión Génica/genética , Humanos , Osteosarcoma/metabolismo , Osteosarcoma/patología , ARN Largo no Codificante/metabolismo , Factores de Transcripción/genéticaRESUMEN
Diabetes is the leading cause of chronic renal failure. Our purpose was to determine the effects of N-nitro-l-arginine (l-NNA) and an extract of Stevia rebaudiana (Bertoni) (SrB) leaves on renal function in streptozotocin-nicotinamide (STZ-NA)-induced diabetic rats. Rats were divided into seven groups. Three of these groups were controls. Diabetes was induced by STZ-NA in the other four. Diabetic rats were treated with SrB (200 mg/kg), L-NNA (100 mg/kg), or SrB + L-NNA for 15 days after 5-8 weeks of diabetes. At the end of the experiments, urine and blood samples were collected from the rats, and kidney tissue samples were collected with the animals under ether anesthesia. Renal filtration changes were determined by measuring urine pH, urine volume, and serum and urine creatinine. Nitric oxide synthase (NOS) activity was measured in kidney homogenates. Alterations in kidney ultrastructure were determined by electron microscopy, and histological changes were examined by hematoxylin and eosin staining. No statistical differences were observed in urine creatinine or creatinine clearance. Even so, we observed higher NOS activity in SrB-treated diabetic rats. SrB-treated diabetic rats had less mitochondrial swelling and vacuolization in thin kidney sections than other diabetic groups. The control groups showed normal histological structure, whereas in the diabetic groups, membrane thickening, tubular epithelial cells, and cellular degeneration were observed. Thus, SrB has beneficial effects on diabetes compared with l-NNA. Our results support the validity of SrB for the management of diabetes as well as diabetes-induced renal disorders.