Circ_0006174 Drives Triple Negative Breast Cancer Progression and Immune Escape Through Regulating miR-3139/PD-L1...

Area of Science:

• Oncology
• Molecular Biology
• Immunology

Background:

• Triple-negative breast cancer (TNBC) is aggressive with limited treatment options.
• The role of circular RNA circ_0006174 in TNBC pathogenesis is currently unclear.
• Circular RNAs are increasingly recognized for their roles in cancer development.

Purpose of the Study:

• To investigate the function and molecular mechanisms of circ_0006174 in TNBC.
• To explore the relationship between circ_0006174, miR-3139, and PD-L1 in TNBC.
• To determine the regulatory role of METTL3-mediated m6A methylation on circ_0006174 in TNBC.

Main Methods:

• In vitro assays (cell counting kit-8, transwell invasion, ELISA, flow cytometry, RNA pull-down, dual-luciferase reporter, RNA immunoprecipitation, western blotting).
• In vivo xenograft models with histological analysis (HE staining, immunohistochemistry).
• Analysis of patient prognosis data associated with circ_0006174 expression.

Main Results:

• Overexpression of circ_0006174 correlates with poor prognosis in TNBC patients.
• Silencing circ_0006174 reduced TNBC cell proliferation, invasion, and PD-L1 expression.
• Circ_0006174 acts as a sponge for miR-3139, upregulating PD-L1; METTL3 regulates circ_0006174 via m6A methylation at position 315.
• In vivo, circ_0006174 inhibition decreased tumor burden and PD-L1, while increasing miR-3139 and IFN-γ.

Conclusions:

• Circ_0006174 promotes TNBC progression via the miR-3139/PD-L1 axis.
• METTL3-mediated m6A methylation is crucial for circ_0006174 function in TNBC.
• Circ_0006174 represents a novel m6A-modified circRNA and a potential therapeutic target for TNBC.