Functional
analysis and therapeutic evaluation of tumorsuppressor miRNA miR-506 in
pancreatic carcinoma
MiRNAs regulate the expression of a wide variety of genes. In the tumor context, tumor-suppressing miRNAs are able to target oncogenes, thus affecting tumor-relevant processes like cell cycle, apoptosis, migration and invasion on multiple levels. They are often under-expressed in tumors and thus of particular interest. The previously largely unknown functions of the tumor suppressor miRNAs miR-24 and miR-506 in pancreatic carcinoma have been elucidated in our recent research.
Based on these results, the project aims at the further exploration of miR-506 with regard to its therapeutic application / clinical translation. For this, the miRNA is transiently transfected into various pancreatic carcinoma cells. Beyond classical 2D cell culture on a plastic surface, more complex multicellular 3D cell/tissue culture models like tumor spheroids and tissue slice cultures are employed as well. Additionally, this project analyses if a miRNA replacement with miR-506 leads to the sensitization of cells towards chemotherapeutics or to what extent the tumor-suppressor function of miR-506 is also observed under conditions of chemoresistance. For these studies, chemoresistant cell lines are now available. For the therapeutic application of the miRNA, polyethylenimine (PEI)-based nanoparticles developed in the Aigner lab will be used as delivery platform, as well as silicon-based nanoparticles (Bio-Courier) provided by the industrial partner SiSaf Ltd. These are tested and compared with regard to efficacy and biocompatibility.
