ABSTRACT
Hepatocellular carcinoma (HCC) is associated with a poor prognosis. Our previous study demonstrated that Pleomorphic adenoma gene like-2 (PLAGL2) was a potential therapeutic target in HCC. However, the mechanisms that lead to the upregulation of PLAGL2 in HCC remain unclear. The present study revealed that stress-induced epinephrine increased the expression of PLAGL2, thereby promoting the progression of HCC. Furthermore, PLAGL2 knockdown inhibited epinephrine-induced HCC development. Mechanistically, epinephrine upregulated ubiquitin-specific protease 10 (USP10) to stabilize PLAGL2 via the adrenergic ß-receptor-2-c-Myc (ADRB2-c-Myc) axis. Furthermore, PLAGL2 acted as a transcriptional regulator of USP10, forming a signaling loop. Taken together, these results reveal that stress-induced epinephrine activates the PLAGL2-USP10 signaling loop to enhance HCC progression. Furthermore, PLAGL2 plays a crucial role in psychological stress-mediated promotion of HCC progression.
Subject(s)
Carcinoma, Hepatocellular , DNA-Binding Proteins , Epinephrine , Gene Expression Regulation, Neoplastic , Liver Neoplasms , RNA-Binding Proteins , Signal Transduction , Transcription Factors , Ubiquitin Thiolesterase , Carcinoma, Hepatocellular/metabolism , Carcinoma, Hepatocellular/pathology , Carcinoma, Hepatocellular/etiology , Carcinoma, Hepatocellular/genetics , Humans , Liver Neoplasms/metabolism , Liver Neoplasms/pathology , Liver Neoplasms/etiology , Liver Neoplasms/genetics , Epinephrine/metabolism , Epinephrine/pharmacology , Signal Transduction/drug effects , RNA-Binding Proteins/metabolism , RNA-Binding Proteins/genetics , Animals , Ubiquitin Thiolesterase/metabolism , Ubiquitin Thiolesterase/genetics , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/genetics , Transcription Factors/metabolism , Transcription Factors/genetics , Gene Expression Regulation, Neoplastic/drug effects , Mice , Cell Line, Tumor , Disease Progression , Male , Stress, Physiological , Cell ProliferationABSTRACT
Cutaneous chronic wounds are characterized by an impaired wound healing which may lead to infection. To surmount this problem, a novel quaternary ammonium chitosan nanoparticles (TMC NPs)/chitosan (CS)composite sponge with asymmetric wettability surfaces was successfully prepared. The optimum concentrations of TMC NPs and CS were 0.2 mg/mL and 2.0%, respectively. The incorporated TMC NPs could improve the antibacterial activity of the CS sponge. Asymmetric modification enables the CS sponge to have hydrophobic outer surface and hydrophilic inner surface. The hydrophobic surface of the sponge shows waterproof and anti-adhesion contaminant properties, whereas the hydrophilic surface preserves water-absorbing capability and efficiently inhibits the growth of bacteria. More importantly, in vivo chronic wound healing model evaluation reveals that TMC NPs/CS composite sponge promotes the wound healing and accelerates re-epithelialization and angiogenesis. And in vivo anti-infection test shows the TMC NPs/CS composite sponge could effectively prevent wound infection. These findings demonstrate that TMC NPs/CS composite sponge is a promising dressing material for chronic wounds.