Effects of PARP inhibition on the transcriptome in BRCA1 wild-type and BRCA1 deficient ovarian cancer cell lines
Despite numerous therapeutic advances over the years, ovarian cancer, especially high grade serous ovarian carcinoma remains the deadliest gynecological malignancy. Although PARP inhibition has been shown to be an effective (maintenance) therapy for homologous recombination repair deficient or BRCA1 mutated ovarian cancer, there may be further potential for combination therapy with other drugs such as immune checkpoint inhibitors. BRCA1 mutation as well as PARP inhibitor (Olaparib) treatment influenced the activation of immune response pathways such as cGAS-STING signaling and Interferon-alpha response in ovarian cancer cell lines. Bioinformatics functional analyses uncovered further immune related cellular responses and signaling pathways such as JAK-STAT signaling. Overall design: To investigate the effect of the PARP inhibitor Olaparib in both BRCA1 wildype (OVCAR3) and BRCA1 mutated (UWB1.289) cells, the IC50 value for 96h treatment with Olaparib in both cell lines was determined. Both cell lines were either treated with Olaparib (determined IC50 value) or vehicle control (DMSO) and harvested for RNA extraction after 96h. This was repeated four times. RNA-seq was done for all samples, raw data was processed and comparative gene expression analyses were conducted.