Effect of MYC and PARP Inhibitors in Ovarian Cancer Using an In Vitro Model

Abstract

Background/aim: The 8q24 chromosomal region, which contains the MYC and PVT1 candidate oncogenes, is amplified in carcinomas. Both genes have been involved in the etiopathogenesis of ovarian cancer (OC). In this study, we used an in vitro OC model with a known 8q24 copy number increase and in silico tools to investigate the expression of MYC/PVT1 loci and copy number variation in OC. We also assessed the effects of rucaparib (a PARP inhibitor) in the presence or absence of 10058F4 (a MYC inhibitor) on the expression of MYC/linear PVT1/circular PVT1.

Materials and methods: Tissue culture, chromosome preparation, RNA extraction, RT-qPCR, FISH, and wound healing assays were employed. OncoDB, cBioportal, UALKAN, and ROC Plotter in silico tools were also utilized.

Results: Although PVT1 and MYC expression levels remained unaltered in OC, putative copy number alterations across all cancers showed a marked difference between the two genes, particularly in gain and amplification for MYC. PVT1 expression demonstrated prognostic value for the treatment of patients with serous and endometrioid OC. Both genes correlated with PARP10, FAM83H, and DEPTOR. The use of rucaparib in the presence or absence of the MYC inhibitor (10058F4) in vitro, led to a significant down-regulation in the expression of MYC, linear, and circular PVT1.

Conclusion: Our data provide a novel insight into the potential interactions of MYC and PVT1 with other genes. Moreover, we identified a new PARP inhibition mechanism down-regulating MYC, as well as the linear and circular PVT1 transcripts. Future work should expand on clinical studies to better understand the prognostic role of PVT1 in OC.

Keywords: MYC; MYC inhibitor; Ovarian cancer; PVT1; circPVT1; rucaparib.