Twist1 silencing suppresses triple-negative breast cancer progression by reducing RNF40 transcription

RING finger protein 40 (RNF40) has been reported to play a key role in cancer development, progression, and metastasis, and may act as an oncogene in triple-negative breast cancer (TNBC). Herein, the oncogenic role and upstream molecular mechanism of RNF40 in TNBC progression were investigated. Detection of mRNA and protein levels was performed using qRT-PCR, western blotting, and immunohistochemical (IHC) staining, respectively. Functional experiments were conducted using colony formation, EdU, flow cytometry, wound healing, transwell, and tube formation assays in vitro, and xenograft mouse models in vivo. The interaction between Twist-related protein 1 (Twist1) and RNF40 was verified by using RNA immunoprecipitation and dual-luciferase reporter assays. RNF40 was highly expressed in TNBC patients and showed a good diagnostic value for TNBC. Its expression was also increased in TNBC cell lines and the silencing of RNF40 suppressed TNBC cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), and angiogenesis as well as induced cell apoptosis in vitro, and hampered TNBC growth and EMT in vivo. Mechanically, Twist1 promoted RNF40 transcription. TNBC tissues and cells also showed a higher Twist1 expression. The deficiency of Twist1 led to a decrease in RNF40 expression, and restrained TNBC cell growth, migration, invasion, EMT, and angiogenesis by regulating RNF40. Twist1 contributed to TNBC cell growth, migration, invasion, EMT, and angiogenesis by promoting RNF40 transcription, suggesting a new insight into the pathogenesis of TNBC.