RESUMO
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.
Assuntos
Carcinoma Hepatocelular , Proteínas de Ligação a DNA , Epinefrina , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas , Proteínas de Ligação a RNA , Transdução de Sinais , Fatores de Transcrição , Ubiquitina Tiolesterase , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/etiologia , Carcinoma Hepatocelular/genética , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/etiologia , Neoplasias Hepáticas/genética , Epinefrina/metabolismo , Epinefrina/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteínas de Ligação a RNA/metabolismo , Proteínas de Ligação a RNA/genética , Animais , Ubiquitina Tiolesterase/metabolismo , Ubiquitina Tiolesterase/genética , Proteínas de Ligação a DNA/metabolismo , Proteínas de Ligação a DNA/genética , Fatores de Transcrição/metabolismo , Fatores de Transcrição/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Camundongos , Linhagem Celular Tumoral , Progressão da Doença , Masculino , Estresse Fisiológico , Proliferação de CélulasRESUMO
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.
