Abstract 2156: Genomics and molecular analysis of Aurora kinase B (AURKB) in response to antiretroviral (ARV) treatment in lung cancer

Abstract

Abstract Aurora kinase B (AURKB) is essential for normal physiological processes. However, aberrant AURKB expression has been reported in various cancers, including lung cancer. Lung cancer is a leading non-AIDS defining cancer (NADCs) and the relationship between the use of antiretrovirals (ARVs) and lung cancer is poorly understood. The anti-proliferative effects of Efavirenz (EFV) and Lopinavir/ritonavir (LPV/r) have also been documented. This study aimed at determining the genomic and molecular roles of AURKB in lung cancer in response to ARV treatment. For this purpose, cellular (xCELLigence RTCA), molecular (RT-qPCR) and bioinformatics tools were used in normal fibroblasts (MRC-5) and adenocarcinoma (A549) lung cells. Real-Time Cell Analysis (RTCA) data confirmed the anti-proliferative effects of ARVs in a time-dependent manner. AURKB gene expression was elevated in A549 compared to MRC-5 in non-ARV treated. Interestingly, p53 and CASP3 gene expression was downregulated. Contrarily, ARV treatment resulted in the formation of a negative signaling loop due to AURKB being downregulated, while CASP3 and p53 were upregulated. KEGG analysis demonstrated AURKB, CASP3 and p53 as cell cycle related genes. STRING database searches showed a strong protein-protein interaction (PPI) between AURKB and p53, and CAP3 and p53, but a weak PPI between AURKB and CASP3. Gene Ontology (GO) analysis revealed a decline in serine/threonine kinase (AURKB) activity in cancer cells in response to ARV treatment. Although not yet confirmed, AURKB displays oncogene features, while its overexpression has been shown to deregulate p53. The association between the use of ARVs and lung carcinogenesis remains to be fully comprehended and targeting AURKB signaling may help shed light on this relationship. Citation Format: Rahaba Makgotso Marima, Rodney Hull, Zodwa Dlamini, Clement Penny. Genomics and molecular analysis of Aurora kinase B (AURKB) in response to antiretroviral (ARV) treatment in lung cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2021; 2021 Apr 10-15 and May 17-21. Philadelphia (PA): AACR; Cancer Res 2021;81(13_Suppl):Abstract nr 2156.