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. Overall design: 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.