miRNA-149* suppresses liver cancer progression by down-regulating TRADD protein expression
Menée in vitro et à l'aide de modèles murins de cancer hépatique, cette étude met en évidence un mécanisme par lequel le microARN 149* supprime la progression tumorale en réduisant l'expression de la protéine TRADD
Liver cancer is the third leading cause of cancer-related death worldwide. Here we show that microRNA-149* (miR-149*) serves as a novel tumor suppressor for liver tumorigenesis. Mice with genetic deletion of miR-149* (miR-149*-/- mice), which caused loss of both miR-149 and miR-149*, were considerably more susceptible to acute liver injury and hepatic carcinogenesis induced by diethylnitrosamine than wild-type mice, accompanied by increased compensatory proliferation and up-regulated gene expression of certain inflammatory cytokines. miR-149* mimics dramatically impaired liver cancer cell proliferation and migration in vitro, and blocked liver cancer progression in a xenograft model. Furthermore, miR-149* strongly suppressed NF-
κB signaling and repressed tumor necrosis factor receptor type 1
–associated DEATH domain protein expression in NF-
κB signaling pathway. These results reveal that miR-149*, as a novel liver tumor suppressor, may serve as a potential therapeutic target for liver cancer treatment.