E2F1 induced neuroblastoma cell migration and invasion via activation of CENPE/FOXM1 signaling pathway

Abstract

Background: Neuroblastoma (NB) is a common malignancy occurring in infants and young children. Centrosome-associated protein E (CENPE) is a kinetochore-related motor protein highly expressed in NB, with the mechanism largely unknown. This study is committed to investigating the role and mechanism of CENPE in NB.Method: Short hairpin RNAs targeting CENPE and E2F transcription factor 1 (shCENPE and shE2F1) and CENPE overexpression plasmid were transfected into IMR-32 and SK-N-SH cells. The mRNA expressions of CENPE, N-Cadherin, Vimentin, and proliferating cell nuclear antigen (PCNA) in NB cells were detected by qRT-PCR. The viability, migration, and invasion of cells were tested through cell function experiments. Western blot was applied to detect the protein levels of N-Cadherin, Vimentin, PCNA, CENPE and Forkhead box M1 (FOXM1). The relationship between CENPE and E2F1 was verified by dual-luciferase reporter assay, while the interaction between FOXM1 and CENPE in NB cells was analyzed by rescue experiments.Results: CENPE expression was upregulated in NB cells from metastatic sites. Silencing of CENPE suppressed the NB cell viability, migration, and invasion; and decreased N-Cadherin, Vimentin and PCNA expressions, while overexpressed CENPE did oppositely. E2F1 positively targeted CENPE and CENPE partly reversed the effects of shE2F1 on repressing NB cell viability, migration, invasion and the activation of CENPE/FOXM1 signaling pathway. In addition, silenced FOXM1 partly offset the effects of CENPE on promoting NB cell migration and invasion.Conclusion: E2F1 induces NB cell migration and invasion via activating CENPE/FOXM1 pathway.