Identification of PRMT5 as a therapeutic target in cholangiocarcinoma [RNA-seq II]

Cholangiocarcinoma is a very aggressive cancer whose incidence is increasing. Moreover, chemotherapies are little effective and the response to immune checkpoint inhibitors is low. We have identified protein arginine-methyltransferase 5 (PRMT5) as a novel therapeutic target in cholangiocarcinoma. Treatment with PRMT5 inhibitor significantly restrains the growth of experimental cholangiocarcinoma model TAZ/AKT without adverse effects. Our findings support the evaluation of PRMT5 inhibitors in clinical trials. To study the effect of PRMT5 inhibition in tumor progression, cholangiocarcinoma (CCA) was induced in C57BL/6J mice by hydrodynamic tail vein injection (HTVI) of plasmids coding for mutant TAZ, myr-AKT and the sleeping beauty transposase (TAZAKT). One group of mice was treated with PRMT5 inhibitor JNJ-64619178 (TAZAKT_JNJ) and control mice received the vehicle (TAZAKT_V). C57BL/6J mice without HTVI injection nor treatment were used as healthy controls (C). We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 different mice of each group.