Effect of protein kinase D inhibition on the transcriptome of epithelial ovarian cancer cells

Epithelial ovarian cancer (EOC) is the most lethal gynaecological malignancy with poor prognosis and high relapse rate. Despite of discovery of several therapeutic approaches including poly-ADP ribose polymerase (PARP) inhibitors, EOC remains highly lethal and warrants early detection and novel therapeutic interventions. Protein kinase D (PKD) isoforms regulate cellular functions associated with tumorigenesis including cell proliferation, migration, invasion but their role in EOC remains unknown. In this study, PKD was inactivated by using pan-PKD inhibitors CRT0066101 and kb-NB142-70 in EOC cell lines OVCAR8 and SKOV3 followed by RNASeq Analysis by Illumina NovaSeq 6000 Sequencing. The data was pooled together to identify differentially expressed genes (DEGs) in each group considered (n=4), filtered with the cut-off of Log2FC +2 for upregulation & -2 for downregulation along with 0.005 of P-value cut off. Our results indicates that PKD abrogation in EOC cells caused differential expression of 4622 genes including KIFC1, KIF22, RAB2A, LAMA5, PLK1, AURKA & PCNA which are majorly involve in cell cycle, membrane trafficking, signal transduction and gene expression. Discovery of these novel PKD-associated proteins\pathways might serve as new therapeutic targets against this lethal pathology.