Silencing LncRNA-DANCR attenuates inflammation and DSS-induced endothelial injury through miR-125b-5p / Silenciar LncRNA-DANCR atenúa la inflamación y la lesión endotelial inducida por DSS a través de miR-125b-5p

Background: LncRNA-DANCR is involved in inflammation and acts as a major contributor to colon cancer. The effects and mechanism of LncRNA-DANCR were first investigated in a DSS-induced colitis model in vivo and vitro. Material and methods: Sprague-Dawley rats were given DSS to induce the colitis model. TNF-α, IL-1β, IL-6 levels and expression of intestinal adhesion proteins ZO-1 and MUC2 in colon tissues and DSS-induced NCM460 cells were measured using corresponding kits. A hematoxylin and eosin (H&E) staining assay was performed to evaluate colon tissue pathology conditions. Protein expression levels in DSS-induced NCM460 cells were evaluated by Western blotting, and cell apoptosis was detected using a TUNEL assay. Gene levels in DSS-induced NCM460 cells were evaluated by PCR. The StarBase online tool was used to predict the LncRNA-DANCR target. The LncRNA-DANCR target was verified using a luciferase reporter assay. Results: LncRNA-DANCR was up-regulated in DSS-induced groups of rats. TNF-α, IL-1β and IL-6 expression was significantly increased in DSS-induced groups of rats and cells. Zo-1 and MUC2 expression levels were decreased in DSS-induced groups of rats. Silencing LncRNA-DANCR reduced inflammation, cell apoptosis and up-regulated ZO-1, MUC2 and Claudin-1 in DSS-induced cells. MiR-125b-5p was the downstream LncRNA-DANCR target. All LncRNA-DANCR effects in the colitis model were reversed by the miR-125b-5p inhibitor. Conclusion: LncRNA-DANCR/miR-125b-5p, which may act as a regulatory axis in inflammation, apoptosis and barrier function dysregulation, can provide an essential reference for the development of new drugs in colitis treatment.(AU)

Antecedentes: LncRNA-DANCR está involucrado en la inflamación y es uno de los mayores contribuyentes al cáncer de colon. Los efectos y el mecanismo de LncRNA-DANCR se investigaron por primera vez en el modelo de colitis inducido por DSS in vivo e in vitro. Material y métodos: Las ratas Sprague-Dawley recibieron DSS para inducir el modelo de colitis. Se midieron el nivel de TNF-α, IL-1, IL-6 y la expresión de proteínas de adhesión intestinal ZO-1 y MUC2 en los tejidos del colon y las células NCM460 inducidas por DSS utilizando los kits correspondientes. Se realizó un ensayo de tinción de hematoxilina y eosina (HE) para la evaluación de las condiciones patológicas del tejido del colon. El nivel de expresión de proteína en las células NCM460 inducidas por DSS se evaluó a través de Western blotting y se detectó apoptosis celular mediante el uso de un ensayo de TUNEL. El nivel genético en las células NCM460 inducidas por DSS se evaluó mediante un ensayo de PCR. La base estelar en línea se aplicó para predecir el objetivo de LncRNA-DANCR. El objetivo de LncRNA-DANCR fue verificado a través del ensayo Luciferase Reporter. Resultados: LncRNA-DANCR fue regulado en grupos inducidos por DSS en ratas. La expresión de TNF-α, IL-1 e IL-6 se incrementó significativamente en grupos inducidos por DSS en ratas y células. El nivel de expresión de Zo-1 y MUC2 disminuyó en los grupos inducidos por DSS en ratas. Silenciar LncRNA-DANCR redujo la inflamación, la apoptosis celular y el ZO-1, MUC2 y Claudin-1 regulados en células inducidas por DSS. MiR-125b-5p era el siguiente objetivo de lncRNA-DANCR. Todos los efectos de LncRNA-DANCR en el modelo de colitis fueron revertidos por el inhibidor miR-125b-5p. Conclusión: El LncRNA-DANCR/miR-125b-5p, que puede ser un eje regulador en la inflamación, la apoptosis y la desregulación de la función de barrera, puede proporcionar una referencia vital para el desarrollo de nuevos fármacos en el tratamiento de la colitis.(AU)

Silencing LncRNA-DANCR attenuates inflammation and DSS-induced endothelial injury through miR-125b-5p.

BACKGROUND: LncRNA-DANCR is involved in inflammation and acts as a major contributor to colon cancer. The effects and mechanism of LncRNA-DANCR were first investigated in a DSS-induced colitis model in vivo and vitro. MATERIAL AND METHODS: Sprague-Dawley rats were given DSS to induce the colitis model. TNF-α, IL-1ß, IL-6 levels and expression of intestinal adhesion proteins ZO-1 and MUC2 in colon tissues and DSS-induced NCM460 cells were measured using corresponding kits. A hematoxylin and eosin (H&E) staining assay was performed to evaluate colon tissue pathology conditions. Protein expression levels in DSS-induced NCM460 cells were evaluated by Western blotting, and cell apoptosis was detected using a TUNEL assay. Gene levels in DSS-induced NCM460 cells were evaluated by PCR. The StarBase online tool was used to predict the LncRNA-DANCR target. The LncRNA-DANCR target was verified using a luciferase reporter assay. RESULTS: LncRNA-DANCR was up-regulated in DSS-induced groups of rats. TNF-α, IL-1ß and IL-6 expression was significantly increased in DSS-induced groups of rats and cells. Zo-1 and MUC2 expression levels were decreased in DSS-induced groups of rats. Silencing LncRNA-DANCR reduced inflammation, cell apoptosis and up-regulated ZO-1, MUC2 and Claudin-1 in DSS-induced cells. MiR-125b-5p was the downstream LncRNA-DANCR target. All LncRNA-DANCR effects in the colitis model were reversed by the miR-125b-5p inhibitor. CONCLUSION: LncRNA-DANCR/miR-125b-5p, which may act as a regulatory axis in inflammation, apoptosis and barrier function dysregulation, can provide an essential reference for the development of new drugs in colitis treatment.