RESUMO
Aquaporin 1 (AQP1) plays an important role in endothelial functions and is regulated by MEF2C. However, how AQP1 level is stabilized to maintain endothelial water homeostasis is still not clear. Here, we show that AQP1 expression is significantly upregulated by MEF2C transcriptionally and inhibited by miR-133a-3p.1 post-transcriptionally. Meanwhile, MEF2C activates the expression of miR-133a1. Simultaneous overexpression of MEF2C and miR-133a-3p.1 suppresses the aptitude of changes in AQP1 expression caused by either MEF2C or miR-133a-3p.1. Accordingly, the changes in migration and tube formation of human umbilical vein endothelial cells (HUVECs) caused by MEF2C or miR133a-3p.1 are blunted by coexpression of both of them. These data demonstrate that the homeostasis and physiological function of AQP1 in endothelial health are maintained by the MEF2C and miR-133a-3p.1 regulatory circuit.
Assuntos
Aquaporina 1/genética , Regulação da Expressão Gênica/genética , Homeostase/genética , Células Endoteliais da Veia Umbilical Humana/metabolismo , MicroRNAs/genética , Água/metabolismo , Sequência de Bases , Movimento Celular/genética , Células Endoteliais da Veia Umbilical Humana/citologia , Humanos , Fatores de Transcrição MEF2/metabolismo , Transcrição GênicaRESUMO
Altered expression of TROP2 is observed in various types of human cancers. However, the clinical significance and pathological role of TROP2 in gallbladder cancer (GBC) remains unclear. The main objective of this investigation was to clarify the relationships between TROP2 expression and the clinicopathological features of patients with GBC. Immunohistochemistry was performed to investigate the expression of TROP2 and epithelial-mesenchymal transition (EMT) indicator proteins in 93 patients with GBC. Immunohistochemistry showed that the protein expression level of TROP2 was significantly higher in GBC tissues than in adjacent noncancerous tissues. In addition, immunohistochemistry analysis showed that TROP2 expression was significantly correlated with histologic grade (P=0.038), tumor stage (P=0.015), and lymph node metastasis (P=0.007). Furthermore, high TROP2 expression was significantly associated with a loss of the epithelial marker E-cadherin (P=0.013) and acquisition of expression of the mesenchymal marker vimentin (P=0.031). Kaplan-Meier analysis and Cox proportional hazards regression models were used to investigate the correlation between TROP2 expression and prognosis of GBC patients. Kaplan-Meier analysis indicated that patients with high TROP2 expression had poor overall survival (P<0.001). Multivariate analysis showed that high TROP2 expression was an independent predictor of overall survival. In conclusion, our data suggest for the first time that the increased expression of TROP2 in GBC is associated significantly with aggressive progression and poor prognosis. In conclusion, this study confirmed that TROP2 might be involved in regulating the EMT and malignant progression in GBC. It also provided the first evidence that TROP2 expression in GBC was an independent prognostic factor of patients, which might be a potential diagnostic and therapeutic target of GBC.
