RESUMEN
Secreted protein acidic and rich in cysteine (SPARC) plays a crucial role in the formation and progression of tumors. DNA methylation has become increasingly recognized as a frequent event of epigenetic alterations and one of the primary mechanisms of gene inactivation. The study aims to investigate the status of DNA methylation and the biofunction of SPARC in breast cancer. The qRT-PCR, BGS, and MSP methods were respectively employed to measure the relative mRNA expression levels and methylation status of SPARC. Additionally, the effects of SPARC on cell proliferation, migration, and invasion were examined in SPARC overexpression and knockdown cells. Immunohistochemical staining and western blot assay were used to examine the protein expression of genes. The expression levels of SPARC were found to be higher in breast cancer tissues and most breast cancer cells. The expression levels of SPARC in MDA-MB-231 and MCF-7 cells were significantly reversed by 5-Aza-dC treatment. Furthermore, the high expression and promoter DNA hypomethylation of SPARC were detected in triple-negative breast cancer tissues, while no expression changes of SPARC were found in luminal A breast cancer tissues. Overexpression of SPARC dramatically promoted MCF-7 cells migration and invasion, while knockdown of SPARC inhibited MDA-MB-231 cells migration and invasion. SPARC was involved in the epithelial-mesenchymal transition (EMT) process of breast cancer cells. The expression levels of mesenchymal markers N-cadherin, Vimentin, and ß-catenin were upregulated, while E-cadherin was downregulated in SPARC overexpressed breast cancer cells. Conversely, the expression levels of EMT-related genes demonstrated the opposite trend in SPARC knockdown cells. To conclude, high expression of SPARC regulated by promoter hypomethylation promotes breast cancer cells migration and invasion, thus SPARC may act as an oncogene and serve as a potential target for breast cancer therapy.
Asunto(s)
Neoplasias de la Mama , Metilación de ADN , Osteonectina/genética , Neoplasias de la Mama Triple Negativas , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular , Proliferación Celular , Transición Epitelial-Mesenquimal , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , Neoplasias de la Mama Triple Negativas/genéticaRESUMEN
INTRODUCTION: Whether anesthesia depth affects postoperative mortality remains uncertain. MEASUREMENTS: Several databases were systematically searched to identify all articles studying the relationship between depth of anesthesia and postoperative mortality. Post hoc subgroup analyses were conducted for follow-up period (30â¯days vs. longer than 90â¯days) and type of surgery. MAIN RESULTS: The analysis included 38,722 patients from nine studies. We observed a significant relationship between low bispectral index (BIS) and mortality (pooled aHR, 1.22;95% CI, 1.08 to 1.38; Pâ¯=â¯0.001; I2â¯=â¯85.4%). Post hoc subgroup analyses indicated low BIS to be linked with significantly elevated mortality risk in patients with ≥90â¯days follow-up (pooled adjusted hazard ratio [aHR], 1.09; 95% CI, 1.00-1.19; Pâ¯=â¯0.01; I2â¯=â¯79.4%), but this association did not achieve significance in those with a 30â¯day follow-up duration (pooled aHR, 1.52; 95% CI, 0.97-2.38; Pâ¯=â¯0.28; I2â¯=â¯79.0%). In addition, this link between postoperative mortality and low BIS was significant in those who had undergone cardiac surgery (pooled aHR, 1.30; 95% CI, 1.14 to 1.49; Pâ¯<â¯0.001; I2â¯=â¯0.0%), but not in patients that had received other forms of surgery (pooled aHR, 1.06; 95% CI, 0.98 to 1.14; Pâ¯=â¯0.14; I2â¯=â¯73.2%). CONCLUSIONS: We observed a significant relationship between deep anesthesia and long-term mortality, though this was not significant 30â¯days following surgery. In patients who had received cardiac surgery, deep anesthesia may increase mortality. However, this trend was not observed in patients who had undergone other forms of surgery.