RESUMEN
Autophagy is a conserved lysosomal degradation pathway where cellular components are dynamically degraded and re-processed to maintain physical homeostasis. However, the physiological effect of autophagy appears to be multifaced. On the one hand, autophagy functions as a cytoprotective mechanism, protecting against multiple diseases, especially tumor, cardiovascular disorders, and neurodegenerative and infectious disease. Conversely, autophagy may also play a detrimental role via pro-survival effects on cancer cells or cell-killing effects on normal body cells. During disorder onset and progression, the expression levels of autophagy-related regulators and proteins encoded by autophagy-related genes (ATGs) are abnormally regulated, giving rise to imbalanced autophagy flux. However, the detailed mechanisms and molecular events of this process are quite complex. Epigenetic, including DNA methylation, histone modifications and miRNAs, and post-translational modifications, including ubiquitination, phosphorylation and acetylation, precisely manipulate gene expression and protein function, and are strongly correlated with the occurrence and development of multiple diseases. There is substantial evidence that autophagy-relevant regulators and machineries are subjected to epigenetic and post-translational modulation, resulting in alterations in autophagy levels, which subsequently induces disease or affects the therapeutic effectiveness to agents. In this review, we focus on the regulatory mechanisms mediated by epigenetic and post-translational modifications in disease-related autophagy to unveil potential therapeutic targets. In addition, the effect of autophagy on the therapeutic effectiveness of epigenetic drugs or drugs targeting post-translational modification have also been discussed, providing insights into the combination with autophagy activators or inhibitors in the treatment of clinical diseases.
Asunto(s)
Autofagia , Procesamiento Proteico-Postraduccional , Procesamiento Proteico-Postraduccional/genética , Autofagia/genética , Fosforilación , Metilación de ADN , Proteínas/genética , Epigénesis Genética/genéticaRESUMEN
MicroRNA-449a (miR-449a) was significantly downregulated in 156 lung cancer tissues (p<0.001). We found that the low expression of miR-449a was highly correlated with cancer recurrence and survival of lung cancer patients. The transient introduction of miR-449a caused cell cycle arrest and cell senescence in A549 and 95D cells. Further studies revealed that E2F3 was a direct target of miR-449a in lung cancer cells. miR-449a also suppressed tumor formation in vivo in nude mice. These results suggest that miR-449a plays an important role in lung cancer tumorigenesis and that miR-449a might predict cancer recurrence and survival of lung cancer patients.
Asunto(s)
Factor de Transcripción E2F3/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Animales , Carcinogénesis/genética , Puntos de Control del Ciclo Celular/genética , Procesos de Crecimiento Celular/genética , Línea Celular Tumoral , Senescencia Celular/genética , Femenino , Genes Supresores de Tumor , Humanos , Neoplasias Pulmonares/patología , Masculino , Ratones , Ratones Endogámicos BALB C , Ratones Desnudos , Persona de Mediana Edad , ARN Interferente Pequeño/administración & dosificación , ARN Interferente Pequeño/genética , TransfecciónRESUMEN
Ti-based biomaterial has been widely used as dental and bone implant material although its bioactivity still needs improvement especially for dental implant. The bone morphogenetic proteins(BMPs) bound to Ti-based materials will attract the mesenchymal stem cells to differentiate into osteoblast cells, which benefits the response to the protein-material surface, and finally leads to new bone formation. Several methods including physically mixing, coating, plasma immobilization and cross-linking were used to investigate how BMPs bind to Ti-based biomaterials. The latest research papers are focused on the structure and function of BMPs, and the methods to bind BMPs to Ti-based biomaterial and the evaluation methods after protein immobilization are reviewed in this paper.
