NCAPD2 promotes breast cancer progression through E2F1 transcriptional regulation of CDK1

Breast cancer (BC) is a serious threat to women's health worldwide. Non-SMC condensin I complex subunit D2 (NCAPD2) is a regulatory subunit of the coagulin I complex, which is mainly involved in chromosome coagulation and separation. The clinical significance, biological behavior, and potential molecular mechanism of NCAPD2 in BC were investigated in this study. We found that NCAPD2 was frequently overexpressed in BC, and it had clinical significance in predicting the prognosis of BC patients. Moreover, loss-of-function assays demonstrated that NCAPD2 knockdown restrained the progression of BC by inhibiting proliferation and migration and enhancing apoptosis in vitro. It was further confirmed that the downregulation of NCAPD2 inhibited tumor growth in vivo. NCAPD2 promoted the progression of BC through the extracellular signal-regulated kinase 5 (ERK5) signaling pathway. Additionally, NCAPD2 could transcriptionally activate CDK1 by interacting with E2F transcription factor 1 (E2F1) in MDA-MB-231 cells. Overexpression of CDK1 alleviated the inhibitory effects of NCAPD2 knockdown in BC cells. In summary, the NCAPD2/E2F1/CDK1 axis may play a role in promoting the progression of BC, which may provide a blueprint for molecular therapy.

Automated summary

This study investigated the clinical significance, biological behavior, and potential molecular mechanism of Non-SMC condensin I complex subunit D2 (NCAPD2) in breast cancer (BC). The findings showed that NCAPD2 was frequently overexpressed in BC and had clinical significance in predicting patient prognosis. Knocking down NCAPD2 inhibited BC progression through inhibiting proliferation and migration and enhancing apoptosis in vitro. Moreover, NCAPD2 downregulation inhibited tumor growth in vivo and promoted BC progression through the ERK5 signaling pathway.