Abstract C092: PRMT1 promotes pancreatic cancer development and resistance to chemotherapy

Abstract

Abstract Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal types of cancer due to the lack of early diagnostic markers and effective therapeutic options. While epigenetic gene regulation is critically involved in the development of various types of cancer, its role in development of PDAC and the potential of therapeutically targeting epigenetic regulators remains underexplored. To identify a targetable epigenetic regulator, we utilized public datasets of pancreatic cancer and show that protein arginine methyl transferase 1 (PRMT1) is highly expressed in pancreatic cancer cells and that high expression of PRMT1 is a poor prognosis factor. Using loss of function studies in vitro and in vivo, we show that PRMT1 is essential for promoting cancer cell proliferation and tumorigenesis. We also demonstrate that the loss of PRMT1 relates to global changes in chromatin accessibility and gene expression pattern. Notably, we revealed that high PRMT1 negatively correlates with gemcitabine sensitivity and exhibit that pharmacological inhibition of PRMT1 in combination with gemcitabine had a greater anticancer effect on pancreatic cancer cells. Collectively, we suggest PRMT1 as a key factor of pancreatic cancer development and a potential candidate of chemotherapy. Citation Format: Bomin Ku, David Eisenbarth, Dae-Sik Lim. PRMT1 promotes pancreatic cancer development and resistance to chemotherapy [abstract]. In: Proceedings of the AACR-NCI-EORTC Virtual International Conference on Molecular Targets and Cancer Therapeutics; 2023 Oct 11-15; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2023;22(12 Suppl):Abstract nr C092.