miR-301a as an NF-κB activator in pancreatic cancer cells.
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.
Duke Scholars
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Related Subject Headings
- Signal Transduction
- Repressor Proteins
- Pancreatic Neoplasms
- Pancreas
- NF-kappa B
- MicroRNAs
- Mice, Nude
- Mice
- Humans
- Gene Expression Regulation, Neoplastic
Citation
Published In
DOI
EISSN
Publication Date
Volume
Issue
Start / End Page
Location
Related Subject Headings
- Signal Transduction
- Repressor Proteins
- Pancreatic Neoplasms
- Pancreas
- NF-kappa B
- MicroRNAs
- Mice, Nude
- Mice
- Humans
- Gene Expression Regulation, Neoplastic