GSE176326
Combinatorial Treatment of Poly (ADP-ribose) Polymerase-1 Inhibitors and Cisplatin Attenuates Cervical Cancer Growth Through FOS-Driven Changes in Gene Expression
Cervical cancer is the one of the most prevalent types of cancers in women and is the second highest cause of death in women aged 20-39.  The most common chemotherapy for cervical cancer involves the use of the drug cisplatin in conjunction with other therapeutics.  However, the development of cisplatin resistance in patients can hinder the efficacy of these treatments.  This highlights the need to explore different therapeutic approaches for cervical cancer treatment.  We found that inhibitors targeting the enzyme Poly (ADP-ribose) Polymearse (PARP)-1 can attenuate cell growth of cervical adenocarcinoma and squamous cell carcinoma.  Furthermore, combinatorial therapy of PARP inhibitors (PARPi) with cisplatin increases the cisplatin-mediated cell toxicity in cervical cancer cells.  This is accompanied by a rewiring of the transcriptome in response to the cisplatin and PARPi together.  Surprisingly, we observed that the Fos gene is upregulated in the dual treatment condition leading to the subsequent induction of its target genes.  Importantly, increased the expression of Fos is sufficient to hinder cervical cancer growth.  We conclude that by inducing Fos expression, PARPi treatment with cisplatin leads to inhibition of cervical cancer. Overall design: RNA-Seq was perfomed in HeLa cells treated with the PARP inhibitor BYK204165  or Cisplatin or both for 6 hours or vehicle control (DMSO).