核因子红细胞源性2相关因子3（Nrf3）在多种癌症中越来越被认为是一种重要的因子，但其在三阴性乳腺癌（TNBC）中的功能尚不清楚。本研究旨在探讨Nrf3在TNBC中的作用。与相邻正常组织相比，TNBC组织中Nrf3的表达水平更高，并且其表达与生存时间呈负相关。此外，Nrf3的敲低减少了TNBC细胞的增殖和迁移能力，而Nrf3的过表达则在体外和体内产生了相反的效果。此外，Nrf3过表达的TNBC细胞的功能富集实验鉴定了数个基因和通路在Nrf3过表达后发生了改变。进一步的研究表明，Nrf3的过表达激活了PI3K/AKT/mTOR信号通路，并调节与上皮间质转化相关的蛋白的表达。通过荧光素酶报告和染色质免疫沉淀实验证实Nrf3直接结合到p110α启动子区域。此外，PI3K抑制剂部分降低了Nrf3过表达的TNBC细胞的增殖和迁移能力。综上所述，Nrf3通过激活PI3K/AKT/mTOR信号通路增强了细胞的增殖和迁移能力，在TNBC中为一种新的治疗靶点。版权所有：© 陈等

Nuclear factor erythroid 2-related factor 3 (Nrf3) is increasingly implicated in multiple types of cancer; however, its function in triple-negative breast cancer (TNBC) remains unclear. This study aimed to examine the role of Nrf3 in TNBC. Compared with adjacent normal tissues, TNBC tissues expressed higher levels of Nrf3, and its expression was negatively correlated with survival time. Additionally, Nrf3 knockdown reduced the proliferation and migration of TNBC cells, whereas overexpression of Nrf3 had the opposite effects in vitro and in vivo. Moreover, functional enrichment of TNBC cells overexpressing Nrf3 allowed for the identification of numerous genes and pathways that were altered following Nrf3 overexpression. Further study showed that overexpression of Nrf3 activated the PI3K/AKT/mTOR signaling pathway and regulated the expression of proteins associated with epithelial-mesenchymal transition. Nrf3 was found to directly bind to p110α promoter regions, as evidenced by luciferase reporter and chromatin immunoprecipitation assays. Furthermore, PI3K inhibitors partially decreased the proliferation and migration of the Nrf3 overexpressing TNBC cells. In conclusion, Nrf3 enhances cellular proliferation and migration by activating PI3K/AKT/mTOR signaling pathways, highlighting a novel therapeutic target for TNBC.Copyright: © Chen et al.