MiR-518c-5p/miR-4524a-3p can mediate immune escape and chemotherapy resistance in triple-negative breast cancer and predict its outcome

  • Hereditas. 2025 Oct 21;162(1):216. doi: 10.1186/s41065-025-00572-8.
Yuan Sun  #  1 ,  Liang An  #  2 ,  Linna Kong  3 ,  Xiaoyan Liu  3 ,  Huihui Zhang  3 ,  Jiaqi Liu  3 ,  Pengfei Qian  4
Affiliations
  • 1. Department of Oncology, Qujing Central Hospital of Yunnan Province (Qujing First People's Hospital), Yunnan, 655000, China.
  • 2. Department of Oncology Surgery, Shanghai Mengchao Cancer Hospital, Shanghai, 200000, China.
  • 3. Department of Breast and Thyroid Surgery, Zibo Central Hospital, Zibo, 255020, China.
  • 4. Department of Breast Surgery, Huizhou Third People's Hospital, Affiliated Hospital of Guangzhou Medical University, No.1 Qiaodong Xuebei Street, Huicheng District, Huizhou, 516001, China. [email protected].
  • # Contributed equally.
PMID: 41121425 DOI: 10.1186/s41065-025-00572-8
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.

Keywords
Chemotherapy resistance; Immune escape; MiR-518c-5p/miR-4524a-3p; Triple-negative breast cancer.
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