hMSH2 coordinated with the expression of E2F1 promotes platinum response in epithelial ovarian cancer

OBJECTIVE: To explore underlying mechanisms that regulate hMSH2 expression and drug susceptibility in epithelial ovarian cancer (EOC). METHODS: Using data from the Cancer Genome Atlas (TCGA) we used bioinformatical analysis to predict transcription factors (TFs) that potentially regulate hMSH2. RT-qPCR, Western blot, and luciferase assays were undertaken using ovarian cancer cell lines to verify the identified TF. Expressions of the TF were modulated using overexpression or knockdown, and the corresponding cellular responses to cisplatin were examined. RESULTS: The TF, E2F1, was found to regulate the hMSH2 gene. The expression level of E2F1 correlated with cisplatin susceptibility in vitro. Kaplan-Meier analysis of 77 patients with EOC showed that low E2F1 expression was associated with worse survival. CONCLUSIONS: To our knowledge, this is the first report of E2F1 regulated MSH2 expression playing a role in drug resistance of platinum-based treatments for patients with EOC. Further work is need to confirm our results.