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Background <p>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.</p> Aim <p>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.</p> Methods <p>Bioinformatics analysis predicted miRNAs targeting <i>HLA-A/B/C</i>, 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.</p> Results <p>MiR-518c-5p/miR-4524a-3p directly targeted <i>HLA-A</i>, <i>HLA-B</i>, and <i>HLA-C</i>, 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.</p> Conclusions <p>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.</p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年10月21日

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  • Yuan Sun,
  • Liang An,
  • Linna Kong,
  • Xiaoyan Liu,
  • Huihui Zhang,
  • Jiaqi Liu,
  • Pengfei Qian

摘要

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.