miR-34a inhibits pancreatic cancer progression through Snail1-mediated epithelial-mesenchymal transition and the Notch signaling pathway

Sci Rep. 2017 Feb 1:7:38232. doi: 10.1038/srep38232.

Abstract

Epithelial-mesenchymal transition (EMT) and Notch signaling are important for the growth and invasion of pancreatic cancer, which is a leading cause of cancer-related deaths worldwide. miR-34a has been shown to play pivotal roles in the progression of several types of cancer. However, little is known about the regulatory mechanisms of miR-34a in pancreatic cancer processes. The aim of this study was to determine whether miR-34a has negative effects on pancreatic cancer and whether these effects are related to EMT and Notch signaling. In vitro, we demonstrated that miR-34a inhibited, while miR-34a inhibitors enhanced, migration and invasion of pancreatic cancer cell lines (PANC-1 and SW-1990).These effects were reversed by Snail1 overexpression or Snail1 shRNA. Furthermore, the anti-apoptotic effects of the miR-34a inhibitors in pancreatic cancer cells were abrogated by Notch1 shRNA. Luciferase reporter assays revealed that the Snail1 and Notch1 genes were direct targets of miR-34a. In vivo, we also demonstrated that miR-34a inhibited pancreatic cancer growth by decreasing Snail1 and Notch1 expression. Therefore, our results indicate that miR-34a inhibits pancreatic cancer progression by post-transcriptionally regulating Snail1 and Notch1 expression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis
  • Cell Line, Tumor
  • Cell Movement
  • Cell Proliferation
  • Disease Progression
  • Epithelial-Mesenchymal Transition*
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • MicroRNAs / metabolism
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • RNA, Small Interfering / genetics
  • Receptor, Notch1 / genetics*
  • Signal Transduction
  • Snail Family Transcription Factors / metabolism*

Substances

  • MIRN34 microRNA, human
  • MicroRNAs
  • NOTCH1 protein, human
  • RNA, Small Interfering
  • Receptor, Notch1
  • SNAI1 protein, human
  • Snail Family Transcription Factors