Germany & USA: PIAS1 is not suitable as a therapeutic agent for urothelial cancer

PIAS1 is not suitable as a urothelial carcinoma biomarker protein and pharmacological target

Holger Hans Hermann Erb, Marlies Ebert, Ronja Kuhn, Lukas Donix, Axel Haferkamp, Robert Ian Seed, Eva Jungel|Department of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, Germany, Department of Urology, Technische Universitat Dresden, Dresden, Germany, National Center for Tumor Diseases (NCT), Partner Site Dresden, Germany: German Cancer Research Center (DKFZ), Heidelberg, Germany; Faculty of Medicine and University Hospital Carl Gustav Carus, Technische Universitat Dresden, Dresden, Germany and Helmholtz Association/Helmholtz-Zentrum Dresden – Rossendorf (HZDR), Dresden, Germany, Department of Pathology, University of California, San Francisco, California, United States of America|2019|PLoS ONE|14:10: e0224085. https://doi.org/10.1371/journal. pone.0224085

Urothelial cancer is one of the most common cancers in Europe. Protein Inhibitor of Activated STAT (PIAS1) has been shown to play an important role in the repair of cisplatin-induced DNA cross-links and radiation-induced DNA strand breaks. PAIS1 can influence activity of various proteins and signally cascades. It has been previously reported that PAIS1 has a role in cancer progression in breast and prostate cancers, however there has been no studies into its role in urothelial cancers. In this study, the role of PIAS1 in urothelial cancers and in the development of treatment resistance was investigated. Three different previously published gene expression microarrays were tested using the Mic qPCR Cycler for mutation rates and expression analysis of PIAS1 in benign and malignant human urothelial tissue. There was found to be no significant different in PIAS1 expression between benign and malignant human urothelial tissue. This was also the case when muscle invasive and non-muscle invasive samples were compared. Screening of commonly used cells lines also revealed no significant differences in the PIAS1 expression and are not involved in DNA repair mechanisms triggered by gamma irradiation. Therefore, the results indicate that PIAS1 plays a minor role in cell survival and DNA repair within urothelial cancer cells in vitro and do not support the role of PIAS1 as a therapeutic target in urothelial cancer.