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

Cancer Gene Therapy volume 22, pages 481–486 (2015)Cite this article

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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.

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Acknowledgements

This project is supported by The Clinical and Translational Science Pilot Grant Program’s Basic Award and Innovative Award at The University of Louisville, and partly by Award Number R03CA137801 from the National Cancer Institute.

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Authors and Affiliations

  1. Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA

    H Pandit, Y Li, S Agle, X Li, S P Li, G Cui & R C G Martin

  2. Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA

    H Pandit & R C G Martin

  3. Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China

    W Zhang

  4. Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic/NB40, Cleveland, OH, USA

    Y Li

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  1. H Pandit
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Correspondence to Y Li or R C G Martin.

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Pandit, H., Zhang, W., Li, Y. et al. Manganese superoxide dismutase expression is negatively associated with microRNA-301a in human pancreatic ductal adenocarcinoma. Cancer Gene Ther 22, 481–486 (2015). https://doi.org/10.1038/cgt.2015.46

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