Abstract
Abstract MIF is a pleiotropic cytokine, which plays a role in inflammatory and immune responses and is implicated in tumorigenesis. Our previous study showed that MIF enhances tumor aggressiveness and predicts outcome in patients with pancreatic ductal adenocarcinoma (PDAC). Aberrant microRNA (miRNA) expression is a common feature in cancer and cytokine responsive miRNAs are recently described as critical effectors in tumor progression. We have investigated MIF-associated miRNAs and their interactive roles in the progression of human pancreatic cancer. Global analysis of miRNA expression revealed 38 differentially expressed miRNAs in MIF-high as compared with MIF-low cases of PDAC based on the median value. Kaplan-Meier survival analysis showed that a higher expression of miR-301b in tumors was associated with poorer survival (p=0.008, N=37), which was further validated in an independent cohort of PDAC patients (p=0.021, N=42). Additionally, MIF expression positively correlated with miR-301b and mediated its expression in several human pancreatic cancer cells. Mechanistic analysis revealed that miR-301b promotes pancreatic cancer cell migration and invasion. Furthermore, nuclear receptor subfamily group c member 2 (NR3C2) was identified as a functional target of miR-301b. NR3C2 inhibited tumor migration and invasion and a higher expression of NR3C2 predicted better survival in pancreatic cancer patients. Further in vivo studies showed a significant decrease in NR3C2 in MIF-overexpressing orthotopic xenograft as compared to control. Taken together, our results demonstrate that MIF and miR-301b interactively contribute to pancreatic cancer progression by targeting NR3C2. This novel MIF-miR-301b-NR3C2 axis may provide potential targets for improving disease outcome in pancreatic cancer. Citation Format: Shouhui Yang, Peijun He, Jian Wang, Aaron Schetter, Naotake Funamizu, Katsuhiko Yanaga, Jochen Gaedcke, B. Michael Ghadimi, Matthias M. Gaida, Thomas Ried, Nader Hanna, H. Richard Alexander, S. Perwez Hussain. Macrophage migration inhibitory factor (MIF) and miR-301b interactively enhance disease aggressiveness by targeting NR3C2 in human pancreatic cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4363. doi:10.1158/1538-7445.AM2014-4363
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
