The oncogenic microRNA miR-21 promotes regulated necrosis in mice.

Published

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