Non-SMC Condensin I Complex Subunit D2 Is a Prognostic Factor in Triple-Negative Breast Cancer for the Ability to Promote Cell Cycle and Enhance Invasion

摘要

Triple-negative breast cancer (TNBC) is a heterogeneous disease with an unfavorable prognosis and no specific targeted therapies. The role of non-SMC condensin I complex subunit D2 (NCAPD2), a regulatory subunit of the condensin I complex that mainly participates in chromosome condensation and segregation, has not been reported in cancer. We therefore evaluated the prognostic value and biological function of NCAPD2 in TNBC. The expression of NCAPD2 was studied in 179 TNBC tissues by immunohistochemistry, and associations among NCAPD2 expression, clinicopathologic features, and the prognosis information of patients with TNBC were analyzed. The mRNA expression profiles of 99 TNBC tissues were also studied, and cell biological behaviors were detected when NCAPD2 was altered in three TNBC cell lines. NCAPD2 expression was positively associated with lymph node metastasis (P = 3.84 x 10(-06)), poor overall survival (P = 0.0033), and worse disease-free survival (P = 0.0013) of patients with TNBC. Moreover, knockdown of NCAPD2 might cause G(2)/M arrest through the p53 signaling pathway, which led to proliferation inhibition, polyploid cell production, and cell apoptosis and inhibited the invasiveness of TNBC cells. For the first time, we report the close association between NCAPD2 and cancer and demonstrate that NCAPD2 plays an important role in TNBC progression and acts as an independent poor prognostic factor and a potential therapeutic target for TNBC.