Polarity protein AF6 functions as a modulator of necroptosis by regulating ubiquitination of RIPK1 in liver diseases.

AF6, a known polarity protein, contributes to the maintenance of homeostasis while ensuring tissue architecture, repair, and integrity. Mice that lack AF6 display embryonic lethality owing to cell-cell junction disruption. However, we show AF6 promotes necroptosis via regulating the ubiquitination of RIPK1 by directly interact with the intermediate domain of RIPK1, which was mediated by the deubiquitylase enzyme USP21. Consistently, while injection of mice with an adenovirus providing AF6 overexpression resulted in accelerated TNFα-induced necroptosis-mediated mortality in vivo, we observed that mice with hepatocyte-specific deletion of AF6 prevented hepatocytes from necroptosis and the subsequent inflammatory response in various liver diseases model, including non-alcoholic steatohepatitis (NASH) and the systemic inflammatory response syndrome (SIRS).Together, these data suggest that AF6 represents a novel regulator of RIPK1-RIPK3 dependent necroptotic pathway. Thus, the AF6-RIPK1-USP21 axis are potential therapeutic targets for treatment of various liver injuries and metabolic diseases.

Research progress on the relationship between miRNA and diagnosis and treatment of gastric cancer / 中国医师杂志

Gastric cancer is one of the most common malignant tumors in China, and its pathogenesis is complex. At present, there is no good method for the diagnosis and treatment of gastric cancer. However, studies have shown that microRNA (miRNA) has abnormal expression in gastric cancer, which participates in the regulation of gastric cancer related genes, and has an impact on the occurrence, development, diagnosis and treatment of gastric cancer. This paper aims to review the relationship between miRNA and the diagnosis and treatment of gastric cancer, as well as the drug resistance in the treatment, so as to lay the foundation for the follow-up research and clinical diagnosis and treatment.