<i>E2F1</i> Silencing Enhances Cisplatin-induced Apoptosis and DNA Damage in Retinoblastoma: <i>CENPE</i> Overexpression as a Compensatory Mechanism

Background: The oncogenic gene E2F transcription factor 1 (<i>E2F1</i>) plays a key role in tumors. This study was designed to explore the effect of <i>E2F1</i> gene expression manipulation and cisplatin on retinoblastoma cells and delineate the underlying mechanism. Methods: <i>E2F1</i> expression in retinoblastoma cells was determined using quantitative real-time polymerase chain reaction (qRT-PCR). After <i>E2F1</i> knockdown, cisplatin-treated cells presenting a malignant phenotype were identified through several methods, such as MTT assay, determination of half-maximal inhibitory concentration (IC₅₀) values, flow cytometry, and comet assay. The effects of <i>E2F1</i> silencing with/without cisplatin on downstream target genes were explored using qRT-PCR and Western blotting. To elucidate the mechanism involving <i>E2F1</i> and centromere protein E (<i>CENPE</i>) in retinoblastoma, rescue experiments were conducted using cells overexpressing <i>CENPE</i>. Results: <i>E2F1</i> was highly expressed in retinoblastoma cells (<i>p</i> < 0.05). <i>E2F1</i> silencing improved the effectiveness of cisplatin in suppressing viability, as well as promoting apoptosis, increasing G1 phase and DNA damage of retinoblastoma cells (<i>p</i> < 0.05). Upregulation of <i>CENPE</i> expression partially reversed the effects of <i>E2F1</i> silencing on cisplatin-treated cells (<i>p</i> < 0.05). Conclusion: <i>E2F1</i> silencing enhances the effect of cisplatin in retinoblastoma by inhibiting <i>CENPE</i>.