The oncogenic microRNA miR-21 promotes regulated necrosis in mice.
Journal Article
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.
Full Text
Duke Authors
Cited Authors
- Ma, X; Conklin, DJ; Li, F; Dai, Z; Hua, X; Li, Y; Xu-Monette, ZY; Young, KH; Xiong, W; Wysoczynski, M; Sithu, SD; Srivastava, S; Bhatnagar, A; Li, Y
Published Date
- May 20, 2015
Published In
Volume / Issue
- 6 /
Start / End Page
- 7151 -
PubMed ID
- 25990308
Pubmed Central ID
- 25990308
Electronic International Standard Serial Number (EISSN)
- 2041-1723
International Standard Serial Number (ISSN)
- 2041-1723
Digital Object Identifier (DOI)
- 10.1038/ncomms8151
Language
- eng