<scp>MTFR1</scp> Promotes Proliferation and Metastasis of Triple‐Negative Breast Cancer by Regulating Mitochondrial Metabolism

Mitochondria, as the center of cellular energy metabolism, play multiple key roles in the progression of triple-negative breast cancer (TNBC). Mitochondrial fission regulator 1 (MTFR1) is a mitochondrial regulatory factor that plays a part in regulating mitochondrial fission and cell development. It is still unknown how MTFR1 functions in TNBC. We discovered MTFR1 to be a crucial gene in TNBC with clinical diagnostic value using database mining analysis. The effects of MTFR1 on TNBC cell proliferation, migration, invasion, and mitochondrial function were determined using the Cell Counting Kit-8, wound healing, and Transwell assays. Nude mouse models were established to explore the impact of MTFR1 on TNBC tumor growth and metastasis. Additionally, western blot and transcriptome sequencing (RNA-seq) were used to investigate the mechanism of MTFR1's involvement in TNBC progression. We used database extraction, WGCNA, Cox regression, and ROC (receiver operating characteristic) curve analysis to identify and confirm MTFR1 as a critical gene in TNBC. In TNBC patients, high MTFR1 expression is related to poor prognosis and diagnostic value. Knockdown of MTFR1 inhibits the proliferation and metastasis of TNBC cells and tumor bodies, affecting mitochondrial function. MTFR1 knockdown inhibits the growth, metastasis, and mitochondrial function of TNBC cells and tumors. Furthermore, transcriptome sequencing and western blot experiments confirmed that MTFR1 knockdown inhibits the activation of the NF-κB signaling pathway. In this study, we report for the first time that MTFR1 is a critical gene upregulated in TNBC. MTFR1 is an oncogene in TNBC and is involved in cell growth, migration, and mitochondrial function, and promotes TNBC progression through the NF-κB signaling pathway. Therefore, targeting MTFR1 may be a promising therapeutic target for TNBC patients.