| First Author | Ma X | Year | 2015 |
| Journal | Nat Commun | Volume | 6 |
| Pages | 7151 | PubMed ID | 25990308 |
| Mgi Jnum | J:224927 | Mgi Id | MGI:5689761 |
| Doi | 10.1038/ncomms8151 | Citation | Ma X, et al. (2015) The oncogenic microRNA miR-21 promotes regulated necrosis in mice. Nat Commun 6:7151 |
| abstractText | MicroRNAs (miRNAs) regulate apoptosis, yet their role in regulated necrosis remains unknown. miR-21 is overexpressed in nearly all human cancer types and its role as an oncogene is suggested to largely depend on its anti-apoptotic action. Here we show that miR-21 is overexpressed in a murine model of acute pancreatitis, a pathologic condition involving RIP3-dependent regulated necrosis (necroptosis). Therefore, we investigate the role of miR-21 in acute pancreatitis injury and necroptosis. miR-21 deficiency protects against caerulein- or L-arginine-induced acute pancreatitis in mice. miR-21 inhibition using locked-nucleic-acid-modified oligonucleotide effectively reduces pancreatitis severity. miR-21 deletion is also protective in tumour necrosis factor-induced systemic inflammatory response syndrome. These data suggest that miRNAs are critical participants in necroptosis and miR-21 enhances cellular necrosis by negatively regulating tumour suppressor genes associated with the death-receptor-mediated intrinsic apoptosis pathway, and could be a therapeutic target for preventing pathologic necrosis. |
