title: Manganese superoxide dismutase expression is negatively associated with microRNA-301a in human pancreatic ductal adenocarcinoma.
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.
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA.|Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: H
authors.initials: H
authors.lastname: Pandit
authors.affiliation: Department of Hand Surgery, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China.
authors.forename: W
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: S
authors.initials: S
authors.lastname: Agle
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: X
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: S P
authors.initials: SP
authors.lastname: Li
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: G
authors.initials: G
authors.lastname: Cui
authors.affiliation: Department of Cancer Biology, Lerner Research Institute, Cleveland Clinic/NB40, Cleveland, OH, USA.
authors.forename: Y
authors.initials: Y
authors.lastname: Li
authors.affiliation: Department of Surgery, Division of Surgical Oncology, University of Louisville School of Medicine, Louisville, KY, USA.|Department of Pharmacology and Toxicology, University of Louisville School of Medicine, Louisville, KY, USA.
authors.forename: R C G
authors.initials: RC
authors.lastname: Martin
mesh_terms: D000818:Animals; D021441:Carcinoma, Pancreatic Ductal / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D015972:Gene Expression Regulation, Neoplastic; D055786:Gene Knockout Techniques; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D035683:MicroRNAs / Q000235:genetics*; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D014183:Transplantation, Heterologous; D047368:Tumor Burden / Q000235:genetics; D000099156:Superoxide Dismutase 2
chemical_list: D035683:MicroRNAs; D013482:Superoxide Dismutase; D000099156:Superoxide Dismutase 2; C550735:MIRN301A microRNA, human