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

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: Differential gene expression analysis of short-read RNA-seq data of 22Rv1 prostate cancer cells treated with 50 nM Lorecivivnt for three days vs. vehicle (DMSO).

细胞周期蛋白依赖性激酶样激酶（Cdc2-like kinase, CLK）家族是剪接过程的调控因子。本研究报道了CLK/DYRK抑制剂洛雷西维特（Lorecivivint, SM04690）对前列腺癌细胞系22Rv1中可变剪接（alternative splicing）的影响。洛雷西维特处理可导致细胞生长受损，并破坏多条致癌通路，包括雄激素应答、MYC及Wnt/β-连环蛋白特征通路。综上，本数据表明可变剪接是前列腺癌发生发展中的关键过程，具备作为治疗靶点的潜力。
整体设计：对经50 nM洛雷西维特处理3天的22Rv1前列腺癌细胞，与溶剂对照（二甲基亚砜，DMSO）组进行短读长RNA测序（short-read RNA-seq）数据的差异基因表达分析。