Targeting the CLK2/SRSF9 splicing axis in prostate cancer leads to decreased ARV7 expression in an rs5918762 allele-dependent manner (ONT long read sequencing)

The Cdc2-like kinase (CLK)-family is a regulator of the splicing process. Here, we report the effect of Lorecivivint (SM04690), a CLK/DYRK inhibitor, on alternative splicing in the prostate cancer cell line 22Rv1. Lorecivivint treatment lead to impaired growth and disruption of several oncogenic pathways, including the androgen response, MYC, and Wnt/ß-catenin hallmark pathways. Taken together, this data shows that alternative splicing is a pivotal process in prostate cancer and is suitable to be targeted. Overall design: Gene expression analysis of long-read RNA-seq data of 22Rv1 prostate cancer cells treated with 50 nM Lorecivivnt for three days vs. vehicle (DMSO).