TFDP1 Enhances the Malignant Biological Behaviors of Breast Cancer Cells by Promoting ASF1B-mediated CKS1B Upregulation

Abstract

Background: Overexpression of the transcription factor Dp-1 (TFDP1) has been demonstrated in breast cancer (BC), indicating a possible involvement in the progression of BC. This study explored the downstream mechanism of TFDP1 in BC. Methods: Quantification of TFDP1, anti-silencing function 1B histone chaperone (ASF1B) and CDC28 protein kinase regulatory subunit 1B (CKS1B) in BC cells was realized through quantitative real-time polymerase chain reaction (qRT-PCR). The relationship among TFDP1, ASF1B and CKS1B was predicted by GEPIA and verified by qRT-PCR and western blot. Through loss- and gain-of-function assays and rescue assays, the effects of TFDP1 and TFDP1/ASF1B/CKS1B axis upon viability, proliferation, migration, and invasion of BC cells were studied. Proliferating cell nuclear antigen (PCNA), matrix metalloproteinases (MMPs) and vimentin protein levels were determined by western blot. Results: TFDP1, ASF1B and CKS1B were highly expressed in BC and were positively correlated in pairs (p < 0.001). TFDP1 overexpression and ASF1B overexpression enhanced while TFDP1/CKS1B/ASF1B silencing suppressed the viability, migration, and invasion of BC cells, and TFDP1 silencing, CKS1B silencing or ASF1B silencing suppressed BC cell viability, migration, and invasion (p < 0.05). TFDP1 silencing suppressed CKS1B and ASF1B expressions (p < 0.05). ASF1B overexpression increased CKS1B, PCNA, MMP-2, MMP-9 and vimentin expression, while these effects were reversed by CKS1B silencing (p < 0.001). Conclusion: TFDP1 facilitates the malignant biological behaviors of BC cells by promoting ASF1B-mediated CKS1B upregulation.