RESUMO
Ras association domain family member 5 (RASSF5), a member of the Ras association domain family, induces cell apoptosis by phosphorylating FOXO3a, which triggers target gene BIM (pro-apoptotic factor) activation. MiR-214 is overexpressed in oral cancer tissue, indicating its possible involvement in oral cancer pathogenesis. Bioinformatics analysis has revealed a complimentary sequence between miR-214 and the 3'-UTR of RASSF5 mRNA. However, whether miR-124 regulates RASSF5 in oral cancer remains poorly understood. We aimed to investigate the role of miR-214 in RASSF5 expression regulation in oral cancer. Tumor and paracarcinoma tissues were obtained from 48 oral cancer patients to examine miR-214 and RASSF5 expression. The relationship between miR-214 and RASSF5 was investigated by dual luciferase reporter gene assay. Oral cancer KB cells were cultured in vitro and divided into inhibitor NC, miR-214 inhibitor, Scramble-pMD18, RASSF5-pMD18, and miR-214 inhibitor + RASSF5-pMD18 groups. Caspase 3 activity, cell apoptosis, and total protein expression were measured by spectrophotometry, flow cytometry, and western blot, respectively. MiR-214 expression was significantly increased, while that of RASSF5 decreased in oral cancer tumor tissues compared to paracarcinoma tissues. Luciferase assay showed that miR-214 suppressed RASSF5 expression by targeting its 3'-UTR. Down-regulation of miR-214 and/or enhancement of RASSF5 expression markedly increased FOXO3a phosphorylation, BIM expression, caspase 3 activity, and apoptosis. In conclusion, miR-214 expression was elevated and RASSF5 was down-regulated in oral cancer. Moreover, miR-214 regulated KB cell apoptosis through targeted inhibition of RASSF5 expression, FOXO3a phosphorylation, and BIM expression, suggesting its possible application as a novel therapeutic oral cancer target.
Assuntos
Apoptose/genética , MicroRNAs/genética , Proteínas Monoméricas de Ligação ao GTP/genética , Neoplasias Bucais/genética , Proteínas Adaptadoras de Transdução de Sinal , Adulto , Idoso , Proteínas Reguladoras de Apoptose/genética , Linhagem Celular Tumoral , Proliferação de Células/genética , Regulação para Baixo , Feminino , Genes Supressores de Tumor , Humanos , Células KB , Masculino , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Proteínas Monoméricas de Ligação ao GTP/metabolismo , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , RNA Mensageiro/genéticaRESUMO
This study evaluates the hemodynamic effects of the administration of 10% pentastarch solution (PS) during the initial treatment of hypovolemia in trauma patients. This prospective randomized phase II study included trauma patients admitted to the emergency room with hemorrhagic hypovolemia: systolic blood pressure (SBP) < 90 mmHg. Upon admission, the patients were randomized to receive 10% PS (n = 12) or isotonic 0.9% NaCl solution (IS) (n = 11), infused intravenously in 250-ml boluses, repeated until SBP > 100 mmHg. Blood pressure, infused volumes necessary to maintain SBP, and overall survival rates were determined and compared between groups. SBP increased significantly following either IS (from 64.4 +/- 9.2 mmHg to 111.1 +/- 6.3 mmHg), or PS (from 63.7 +/- 10.6 mmHg to 108.1 +/- 9.8 mmHg) when compared to admission values (p < 0.05). Endovenous volumes infused were greater (p = 0.001) in IS patients (1420 +/- 298 ml) than in PS patients (356 +/- 64 ml). No blood was transfused into PS patients, compared to 370 +/- 140 ml of red blood cells transfused into IS patients (p = 0.015). Mortality rates were similar in the two groups (p = 0.725). We concluded that PS is a safe, efficient method for inducing hemodynamic recovery of hypovolemic trauma patients, with a clear reduction in the intravenous volumes required for acute resuscitation.