miR-210 regulates the interaction between pancreatic cancer cells and stellate cells

Biochem Biophys Res Commun. 2013 Aug 2;437(3):433-9. doi: 10.1016/j.bbrc.2013.06.097. Epub 2013 Jul 4.

Abstract

There is accumulating evidence that pancreatic stellate cells (PSCs) promote the progression of pancreatic cancer. microRNAs (miRNAs) are small non-coding RNAs acting as negative regulators of gene expression at the post-transcriptional level. This study aimed to clarify the role of miRNAs in the interaction between PSCs and pancreatic cancer cells. Pancreatic cancer cells were mono-cultured or indirectly co-cultured with PSCs. miRNAs were prepared, and Agilent's miRNA microarray containing probes for 904 human miRNAs was used to identify differentially expressed miRNAs. miR-210 was identified as an upregulated miRNA by co-culture with PSCs. Conditioned media of PSCs activated ERK and Akt, but not hypoxia-inducible factor-1α pathway. PSCs-induced miR-210 upregulation was inhibited by inhibitors of ERK and PI3K/Akt pathways. Inhibition of miR-210 expression decreased migration, decreased the expression of vimentin and snai-1, and increased the membrane-associated expression of β-catenin in Panc-1 cells co-cultured with PSCs. In conclusion, our results suggest a novel role of miR-210 in the interaction between PSCs and pancreatic cancer cells.

Keywords: 4′, 6-diamidino-2-phenylinodole; 5-bromo-2′-deoxyuridine; BrdU; DAPI; EMT; Fibrosis; HIF; MicroRNA; OD; PSC-CM; PSCs; Pancreatic cancer; Pancreatitis; Stroma; conditioned medium of hPSC21-S/T cells; epithelial-mesenchymal transition; hypoxia-inducible factor; miRNA; micro RNA; optical density; pancreatic stellate cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Communication / genetics
  • Cell Line, Tumor
  • Cell Transformation, Neoplastic / genetics*
  • Coculture Techniques
  • Gene Knockdown Techniques
  • Humans
  • Hypoxia / genetics
  • Hypoxia / metabolism
  • Hypoxia / pathology
  • MicroRNAs / antagonists & inhibitors
  • MicroRNAs / biosynthesis
  • MicroRNAs / genetics*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology*
  • Pancreatic Stellate Cells / cytology
  • Pancreatic Stellate Cells / metabolism*
  • Pancreatic Stellate Cells / pathology

Substances

  • MIRN210 microRNA, human
  • MicroRNAs