miR-301a幻灯片.pptVIP

miR-301a as an NF-κB activator in pancreatic cancer cells 化工112硕 周小军 Introduction to Dr.Yong Li Department of Biochemistry and Molecular Biology, University of Louisville, Louisville, KY, USA Research Interests: MicroRNAs; The focus of Dr. Li’s laboratory is to investigate the biological and pathological functions of MicroRNAs. Content Abstract Introduction Results Discussion 1 Abstract This novel mechanism of NF-κB activation by an miRNA offers new avenues for therapeutic interventions against pancreatic cancer. 2 Introduction NF-κB is a transcription factor (TF) consisting of dimers of NF-κB1 (p50), NF-κB2, RelA, RelB, and c-Rel proteins. MicroRNAs (miRNAs) are short 20–25 nt RNA molecules that negatively regulate gene expression in animals and plants. We first found that miR-301a is specifically up-regulated in pancreatic cancer. Activates NF-κB by negatively regulating the expression of the NF-κB-repressing factor (Nkrf) gene. We also found that the expression of miR-301a is up-regulated when NF-κB is activated. MiR-301a inhibition or Nkrf overexpression in pancreatic cancer cells led to reduced NF-κB activation and tumour growth. Indicating that this NF-κB activation mechanism could be a target for therapeutic intervention against pancreatic adenocarcinoma. 3 Results miR-301a as the most potent NF-κB activator miR-301a targets Nkrf miR-301a expression is regulated by NF-κB Down-regulation of miR-301a in pancreatic cancer cells reduces NF-κB activation Nkrf is expressed at a lower level in pancreatic tumours than normal pancreas tissues miR-301a inhibition reduces xenograft tumour growth 3.1 miR-301a as the most potent NF-κB activator We constructed an miRNA genetic library that is based on a feline immunodeficiency virus vector. Formulate a reporter strategy to screen miRNAs from this library that modulate NF-κB activation. When all the miRNA constructs in the library were screened with the first assay, w