Manganese superoxide dismutase expression is negatively associated with microRNA-301a in human pancreatic ductal adenocarcinoma

Cancer Gene Ther. 2015 Oct;22(10):481-6. doi: 10.1038/cgt.2015.46. Epub 2015 Sep 18.

Abstract

Manganese superoxide dismutase (MnSOD) expression has been found to be low in human pancreatic ductal adenocarcinoma (PDAC). Previously, we have reported that microRNA-301a (miR-301a) was found being upregulated via nuclear factor-κB (NF-κB) feedback loop in human PDAC. In this study, we investigate whether the miR-301a expression level is associated with MnSOD expression in human PDAC. We established a xenograft PDAC mouse model using transfected PanC-1 cells (miR-301a antisense or scrambled control) to investigate tumor growth and the interaction between MnSOD and miR-301a. The animal study indicated that miR-301a antisense transfection could significantly decrease the growth rate of inoculated PDAC cells, and this decrease in tumor growth rate is associated with increased MnSOD expression. To evaluate the MnSOD-miR-301a correlation in human PDAC, we have analyzed a total of 60 PDAC specimens, along with 20 normal pancreatic tissue (NPT) specimens. Human specimens confirmed a significant decrease of MnSOD expression in PDAC specimens (0.88±0.38) compared with NPT control (2.45±0.76; P<0.05), whereas there was a significant increase in miR-301a levels in PDAC specimens (0.89±0.28) compared with NPT control (0.25±0.41; P<0.05). We conclude that MnSOD expression is negatively associated with miR-301a levels in PDAC tissues, and lower miR-301a levels are associated with increased MnSOD expression and inhibition of PDAC growth.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Carcinoma, Pancreatic Ductal / genetics*
  • Carcinoma, Pancreatic Ductal / metabolism
  • Carcinoma, Pancreatic Ductal / pathology
  • Cell Line, Tumor
  • Gene Expression Regulation, Neoplastic
  • Gene Knockout Techniques
  • Humans
  • Immunohistochemistry
  • In Situ Hybridization
  • Mice, Inbred BALB C
  • Mice, Nude
  • MicroRNAs / genetics*
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / metabolism
  • Pancreatic Neoplasms / pathology
  • Superoxide Dismutase / genetics*
  • Superoxide Dismutase / metabolism
  • Transplantation, Heterologous
  • Tumor Burden / genetics

Substances

  • MIRN301A microRNA, human
  • MicroRNAs
  • Superoxide Dismutase
  • superoxide dismutase 2