Abstract

Background: Triple-negative breast cancer (TNBC), is characterized by its highly aggressive nature, with chemotherapy resistance and immune evasion contributing to poor outcomes. The role of major histocompatibility complex class I (MHCI) downregulation in TNBC progression remains incompletely understood.

Aim: The present research focused on elucidating the roles of miR-518c-5p/miR-4524a-3p in immune evasion and chemoresistance in TNBC, and evaluating their clinical significance.

Methods: Bioinformatics analysis predicted miRNAs targeting HLA-A/B/C, validated by dual-luciferase assays. Functional studies in TNBC cell lines (MDA-MB-231/468 and ADR-resistant sublines) included chromium release, proliferation, invasion, and apoptosis assays. Clinical relevance was assessed in 88 TNBC patients and 88 controls using RT-PCR and survival analysis.

Results: MiR-518c-5p/miR-4524a-3p directly targeted HLA-A, HLA-B, and HLA-C, downregulating MHCI expression and promoting immune evasion. Overexpression of miR-518c-5p/miR-4524a-3p enhanced TNBC cell proliferation, invasion, and chemoresistance to doxorubicin, while their inhibition reversed these effects. High expression of miR-518c-5p/miR-4524a-3p correlated with adverse clinical outcomes in TNBC patients, including shorter recurrence-free survival.

Conclusions: MiR-518c-5p/miR-4524a-3p contribute to TNBC progression by facilitating immune evasion and chemoresistance. Targeting miR-518c-5p/miR-4524a-3p may represent a promising therapeutic approach for improving TNBC treatment outcomes.