affects sensitivity to cisplatin and BCNU but not to paclitaxel in MDA-MB-231 breast cancer cells.

Breast cancer has the highest incidence of all cancer types in women. Triple-negative breast cancer (TNBC) accounts for 15% of all breast cancer cases and is the most aggressive type, with a poor prognosis and limited treatment. Treatment failure in patients is largely due to resistance to chemotherapy. In this study, we aimed to identify the novel factors contributing to chemoresistance in TNBC using cisplatin and 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU). We found that transactivation of the heme-binding protein 2 () gene was common in surviving colonies of cells after exposure to two types of chemotherapeutic agents, namely cisplatin and BCNU, from genome-scale transcriptional activation library screening in the TNBC cell line MDA-MB-231. Analysis of a public database (Proteogenomic Landscape of Breast Cancer, CPTAC) indicated that mRNA expression was elevated in TNBC tissues compared to that in non-TNBC tissues. facilitates necrotic cell death under oxidative stress; however, it is not yet known whether affects cancer cell survival following chemotherapy. Therefore, we investigated the effects of expression on the sensitivity to cisplatin and BCNU in MDA-MB-231 cells. Overexpression of significantly enhanced the viability of MDA-MB-231 cells in response to cisplatin and BCNU, but not methyl methanesulfonate (MMS) and paclitaxel. In contrast, CRISPR/Cas9-mediated -knockout greatly reduced cell viability in response to cisplatin and BCNU, but not to MMS and paclitaxel, in MDA-MB-231 cells. Moreover, the exogenous introduction of restored the resistance of -deficient cells to cisplatin and BCNU to wild-type levels. These findings suggest that may play a significant role in resistance to cisplatin and BCNU, which induce intrastrand and interstrand DNA crosslinks, but not to monoalkylating or microtubule-stabilizing agents in TNBC cells. The possibility exists that serves as a biomarker for predicting response or a therapeutic target for overcoming resistance to platinum-based and alkylating anticancer agents in TNBC.