miR-301a as an NF-κB activator in pancreatic cancer cells.

Journal Article (Journal Article)

NF-κB is constitutively activated in most human pancreatic adenocarcinoma, which is a deadly malignancy with a 5-year survival rate of about 5%. In this work, we investigate whether microRNAs (miRNAs) contribute to NF-κB activation in pancreatic cancer. We demonstrate that miR-301a down-regulates NF-κB-repressing factor (Nkrf) and elevates NF-κB activation. As NF-κB promotes the transcription of miR-301a, our results support a positive feedback loop as a mechanism for persistent NF-κB activation, in which miR-301a represses Nkrf to elevate NF-κB activity, which in turn promotes miR-301a transcription. Nkrf was found down-regulated and miR-301a up-regulated in human pancreatic adenocarcinoma tissues. Moreover, miR-301a inhibition or Nkrf up-regulation in pancreatic cancer cells led to reduced NF-κB target gene expression and attenuated xenograft tumour growth, indicating that miR-301a overexpression contributes to NF-κB activation. Revealing this novel mechanism of NF-κB activation by an miRNA offers new avenues for therapeutic interventions against pancreatic cancer.

Full Text

Duke Authors

Cited Authors

  • Lu, Z; Li, Y; Takwi, A; Li, B; Zhang, J; Conklin, DJ; Young, KH; Martin, R; Li, Y

Published Date

  • January 5, 2011

Published In

Volume / Issue

  • 30 / 1

Start / End Page

  • 57 - 67

PubMed ID

  • 21113131

Pubmed Central ID

  • PMC3020116

Electronic International Standard Serial Number (EISSN)

  • 1460-2075

Digital Object Identifier (DOI)

  • 10.1038/emboj.2010.296

Language

  • eng

Conference Location

  • England