MiR-301a as an NF-?B activator in pancreatic cancer cells.

ABSTRACT: NF-?B 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-?B activation in pancreatic cancer. We demonstrate that miR-301a down-regulates NF-?B-repressing factor (Nkrf) and elevates NF-?B activation. As NF-?B promotes the transcription of miR-301a, our results support a positive feedback loop as a mechanism for persistent NF-?B activation, in which miR-301a represses Nkrf to elevate NF-?B 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-?B target gene expression and attenuated xenograft tumour growth, indicating that miR-301a overexpression contributes to NF-?B activation. Revealing this novel mechanism of NF-?B activation by an miRNA offers new avenues for therapeutic interventions against pancreatic cancer.

SUBMITTER: Lu Z 

PROVIDER: S-EPMC3020116 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature