Mussalam L Alabdullah1,2*, Adel Alblihy1,3, Reem Ali1, Stephen Chan1, Srinivasan Madhusudan1,4 and Emad A Rakha1
1Translational Oncology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham Biodiscovery Institute, UK
2Department of Pediatric Surgery, Leicester University Teaching Hospitals NHS Trust, UK
3Medical Centre, King Fahad Security Collage (KFSC), Saudi Arabia
4Department of Oncology, Nottingham University Hospitals, UK
Background: DNA Damage Repair (DDR) proteins play crucial roles in tumour behavior. LIG3 is key cell DDR element. This study evaluates the impact of LIG3 subcellular localization in primary Ovarian Cancer (OC) patients who were treated by upfront surgery.
Methods: LIG3 nuclear and cytoplasmic expression was assessed pre-clinically by performing nuclear and cytoplasmic extraction on A2780 (Platinum sensitive) and A2780Cis (Platinum resistant) OC cell lines. Western blot was utilized to identify the representative protein bands. GraphPad Prism software was utilized to perform the analysis.
Results: After 48 h of incubation with cisplatin, A2780 cells showed a significant increase in LIG3 cytoplasmic fraction, (p-value = 0.0072) compared to the untreated cells. Similarly, in A2780Cis an increase in cytoplasmic fraction of LIG3 was observed but it did not reach a statistically significant value, (p-value = 0.2854). On the other hand, the nuclear isoform of LIG3 did not show any
statistically significant change in both platinum sensitive and resistant cell lines, (p-value = 0.1014) and (p-value = 0.7510) respectively.
Conclusion: Human cytoplasmic LIG3 has crucial role in OC progression and can potentially predict patients’ outcome and resistance to platinum chemotherapeutic agents. The data presented here reveal novel findings with vital clinical applications that could be used for future patients’ treatment categorizations.
DNA repair; LIG3; Nuclear; Cytoplasmic
Alabdullah ML, Alblihy A, Ali R, Chan S, Madhusudan S, Rakha EA. Human Ligase 3 (LIG3) Impact on Primary Surgically Resected Epithelial Ovarian Cancer is Dependent on Its Cellular Sub-Localization - Clinical and Preclinical Evaluation. Clin Oncol. 2022;7:1890..