MicroRNA targets autophagy in pancreatic cancer cells during cancer therapy

Autophagy. 2013 Dec;9(12):2171-2. doi: 10.4161/auto.26463. Epub 2013 Oct 8.

Abstract

The therapeutic outcome of pancreatic cancer is generally poor due to the inherent or acquired resistance of cancer cells to treatment. Pancreatic cancer cells have higher basal autophagy levels than other cancer cell types, which may correlate with their nonresponsiveness to the available cancer therapy. Therefore, understanding the mechanisms behind autophagy activation in pancreatic cancer cells may ultimately improve therapeutic outcomes. Here we demonstrated that MIR23B is a potent inhibitor of autophagy. MIR23B targets the 3?UTR of the autophagy-related gene ATG12, thereby decreasing autophagic activity and ultimately promoting radiation-induced pancreatic cancer cell death. Thus, our study clarified some of the underlying molecular mechanisms of activated autophagy in response to cancer therapy in pancreatic cancer.

Keywords: ATG12; autophagy; microRNA; pancreatic cancer; radiosensitivity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autophagy / genetics*
  • Autophagy / radiation effects
  • Autophagy-Related Protein 12
  • Cells, Cultured
  • Combined Modality Therapy
  • Gene Targeting
  • Genetic Therapy
  • Humans
  • MicroRNAs / physiology*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / radiotherapy
  • Pancreatic Neoplasms / therapy*
  • Radiation Tolerance / genetics
  • Small Ubiquitin-Related Modifier Proteins / antagonists & inhibitors
  • Small Ubiquitin-Related Modifier Proteins / genetics

Substances

  • ATG12 protein, human
  • Autophagy-Related Protein 12
  • MIRN23a microRNA, human
  • MicroRNAs
  • Small Ubiquitin-Related Modifier Proteins