RESUMEN
Ubiquitin specific peptidase 39 (USP39) serves important roles in mRNA processing and is involved in tumorigenesis of multiple solid malignancies. However, the influence and underlying mechanism of USP39 on human renal cell carcinomas (RCC) remain to be elucidated. The current study investigated the functional roles of USP39 in human RCC cell lines. siRNAmediated RNA interference was used to downregulate USP39 in RCC cells. CCK8, wound healing and invasion assays were performed to assess the proliferative ability and metastatic potential. The cell cycle distribution and apoptosis were evaluated by flow cytometry. The activity of signaling pathways and the expression of cell cyclerelated proteins were detected by western blot analysis. The siRNAdirected RNA interference targeting USP39 could effectively downregulate the expression level of USP39 in two RCC cell lines. Depletion of USP39 by siRNA significantly suppressed cell growth and decreased invasive capacity of RCC cells. Silencing of USP39 induced cell apoptosis and cell cycle arrest at G2/M phase. Additionally, the expression levels of apoptotic and G2/M phaserelated proteins were notably decreased following depletion of USP39. Mechanistically, downregulation of USP39 blocked the activation of Akt and extracellular signal regulated kinase signaling pathways in RCC cells. These findings indicate that USP39 may serve as an oncogenic factor in RCC and could be a potential therapeutic candidate for human RCCs.
Asunto(s)
Proliferación Celular , Proteasas Ubiquitina-Específicas/metabolismo , Apoptosis , Carcinoma de Células Renales/metabolismo , Carcinoma de Células Renales/patología , Línea Celular Tumoral , Movimiento Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Puntos de Control de la Fase G2 del Ciclo Celular , Humanos , Neoplasias Renales/metabolismo , Neoplasias Renales/patología , Puntos de Control de la Fase M del Ciclo Celular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Interferencia de ARN , ARN Interferente Pequeño/metabolismo , Transducción de Señal , Proteasas Ubiquitina-Específicas/antagonistas & inhibidores , Proteasas Ubiquitina-Específicas/genéticaRESUMEN
AIM: To investigate the effects of naringenin eye drops on N-methyl-N-nitrosourea (MNU)-induced photoreceptor cell death in rats. METHODS: Photoreceptor cell death was induced by single intraperitoneal injection of MNU (60 mg/kg) in rats. Both eyes of all animals were instilled with one drop of vehicle, 0.5% or 1.0% naringenin eye drops three times per day from 7d before to 17d after MNU injection. Effects of naringenin on MNU-induced photoreceptor cell death were evaluated by electrophysiological and histological analysis. RESULTS: Flash electroretinography (FERG) and oscillatory potentials (OPs) recordings showed that the vehicle control group had remarkable reduction of amplitudes and prolongation of latency times. FERG and OPs responses were significantly reversed in MNU-induced rats treated with 0.5% or 1.0% naringenin eye drops compared with the vehicle control. The retinal morphological results showed that naringenin dose-dependently preserved the outer nuclear layer, outer retina and total retina. CONCLUSION: These results indicate that topical treatment with naringenin eye drops prevented retinal neurons from MNU-induced structural and functional damages.