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

Area of Science:

• Oncology
• Molecular Biology
• Cancer Genetics

Background:

• RING finger protein 40 (RNF40) is implicated in cancer, potentially acting as an oncogene in triple-negative breast cancer (TNBC).
• Understanding the upstream regulators and precise role of RNF40 in TNBC is crucial for developing targeted therapies.

Purpose of the Study:

• To investigate the oncogenic role of RNF40 in TNBC progression.
• To elucidate the upstream molecular mechanism regulating RNF40 expression in TNBC.

Main Methods:

• Quantitative real-time PCR (qRT-PCR), Western blotting, and immunohistochemistry (IHC) for RNF40 and Twist1 detection.
• In vitro assays (colony formation, EdU, flow cytometry, wound healing, transwell, tube formation) and in vivo xenograft models to assess TNBC cell behavior.
• RNA immunoprecipitation and dual-luciferase reporter assays to confirm the interaction between Twist1 and RNF40.

Main Results:

• RNF40 was highly expressed in TNBC patients and cell lines, demonstrating diagnostic value.
• Silencing RNF40 inhibited TNBC cell proliferation, migration, invasion, epithelial-mesenchymal transition (EMT), angiogenesis, and induced apoptosis in vitro, and suppressed tumor growth in vivo.
• Twist-related protein 1 (Twist1) was found to promote RNF40 transcription, and Twist1 deficiency reduced RNF40 expression and suppressed TNBC progression.

Conclusions:

• RNF40 acts as an oncogene in TNBC, driving tumor progression through multiple cellular processes.
• Twist1 promotes TNBC growth, migration, invasion, EMT, and angiogenesis by upregulating RNF40 transcription.
• The Twist1-RNF40 axis represents a novel molecular mechanism and potential therapeutic target in TNBC pathogenesis.