TRIM32 promotes proliferation and confers chemoresistance to breast cancer cells through activation of the NF-κB pathway.

Dysregulation of TRIM32 has been implicated in several human cancers, however, its clinical significance and biological function in breast cancer have not been investigated. Using immunohistochemistry, we found that TRIM32 expression is upregulated in breast cancer tissues and that it correlates with advanced stage and poor prognosis. TRIM32 is also overexpressed in 4/7 breast cancer cell lines. CCK8 and colony formation assays showed that TRIM32 depletion inhibited proliferation and colony formation in the T47D cell line, while TRIM32 overexpression promoted MCF-7 cell growth and colony formation. Cell viability and Annexin V/PI staining demonstrated that TRIM32 maintained breast cancer cell survival and reduced apoptosis rate when cells were treated with cisplatin. Western blot analysis demonstrated that TRIM32 overexpression resulted in an upregulation of p-IκB, p-p65, cIAP1, and cIAP2 and a downregulation of p21 and p27 in MCF-7 cells. TRIM32 depletion in T47D cells demonstrated the opposite results, suggesting that TRIM32 may activate the NF-κB pathway. The NF-κB inhibitor BAY 11-7082 blocked the effects of TRIM32 on cisplatin resistance and cIAP1/2 protein regulation. Taken together, the present study demonstrates that TRIM32 downregulates p21/p27 and upregulates IAP family proteins to facilitate breast cancer cell growth and inhibit drug-induced apoptosis, possibly through the NF-κB signaling pathway.