Abstract 1089: Cardiac glycosides affect miRNA expression profiles in renal cell carcinoma cell lines

Abstract

Abstract Background: Renal Cell Carcinoma (RCC) is the ninth most common cancer worldwide, with about 338,000 new cases diagnosed in 2012. Especially metastatic renal cell carcinoma has still despite surgical cytoreduction, VEGF-tyrosine kinase inhibitors, mTOR inhibitors and first promising results of immunotherapies a very poor prognosis what implies an urgent need for additional therapies. Cardiac glycosides have come into the focus as potential cancer treatment option. They can have anti-proliferative and apoptotic characteristics in several cancer cell lines but affect only in a much lesser extent normal cell lines. MicroRNAs are small non-coding RNAs of 17-25 nucleotides length that widely exist and they play an important regulating role in many normal and pathophysiological cellular processes, as cell proliferation, differentiation, induction of apoptosis, tumorigenesis and tumor progression. Material and Methods: Four renal cell carcinoma cell lines were treated with three different cardiac glycosides in the IC50 concentrations during 72h. For the investigation of miRNA expression miRNA microarray expression analyses were performed. In silico target gene and pathway enrichment analyses were performed. Results: An overlap between all treatments and all cell lines could be detected for two mature miRNAs and two premature miRNAs. Pathway enrichment analysis identified MAPK and axon guidance pathways. Moreover, we looked for genes predicted to be regulated by the deregulated miRNAs in all cell lines at all treatments in the MAPK and the axon guidance pathways. Conclusion: The identification and characterization of deregulated miRNAs after cardiac glycoside treatment could give insight in their gene regulation and thus help to clarify the molecular basis of their anti-proliferative and apoptotic effects. Citation Format: Elke Nolte, Sven Wach, Izabella T. da Silva, Arif Ekici, Frieder Müller-Uri, Wolfgang Kreis, Julio Vera-Gonzales, Bernd Wullich, Helge Taubert, Xin Lai. Cardiac glycosides affect miRNA expression profiles in renal cell carcinoma cell lines. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 1089.