期刊
CANCER GENE THERAPY
卷 22, 期 10, 页码 481-486出版社
NATURE PUBLISHING GROUP
DOI: 10.1038/cgt.2015.46
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资金
- University of Louisville
- National Cancer Institute [R03CA137801]
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-kappa B (NF-kappa B) 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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