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

IF 2.5 3区生物学

Hereditas Pub Date : 2025-10-21 DOI:10.1186/s41065-025-00572-8

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

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引用次数: 0

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.

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MiR-518c-5p/miR-4524a-3p可介导三阴性乳腺癌的免疫逃逸和化疗耐药并预测其预后。

背景：三阴性乳腺癌（TNBC）的特点是具有高度侵袭性，化疗耐药和免疫逃避导致预后不良。主要组织相容性复合体I类（MHCI）下调在TNBC进展中的作用尚不完全清楚。目的：本研究旨在阐明miR-518c-5p/miR-4524a-3p在TNBC免疫逃避和化疗耐药中的作用，并评价其临床意义。方法：生物信息学分析预测靶向HLA-A/B/C的mirna，并通过双荧光素酶检测验证。TNBC细胞系（MDA-MB-231/468和耐药亚系）的功能研究包括铬释放、增殖、侵袭和凋亡测定。采用RT-PCR和生存分析对88例TNBC患者和88例对照组进行临床相关性评估。结果：MiR-518c-5p/miR-4524a-3p直接靶向HLA-A、HLA-B、HLA-C，下调MHCI表达，促进免疫逃避。过表达miR-518c-5p/miR-4524a-3p可增强TNBC细胞的增殖、侵袭和对阿霉素的化疗耐药，而抑制miR-4524a-3p可逆转这些作用。miR-518c-5p/miR-4524a-3p的高表达与TNBC患者的不良临床结果相关，包括更短的无复发生存期。结论：MiR-518c-5p/miR-4524a-3p通过促进免疫逃避和化疗耐药促进TNBC的进展。靶向miR-518c-5p/miR-4524a-3p可能是改善TNBC治疗结果的一种有希望的治疗方法。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Hereditas Biochemistry, Genetics and Molecular Biology-Genetics

CiteScore

3.80

自引率

3.70%

发文量

期刊介绍： For almost a century, Hereditas has published original cutting-edge research and reviews. As the Official journal of the Mendelian Society of Lund, the journal welcomes research from across all areas of genetics and genomics. Topics of interest include human and medical genetics, animal and plant genetics, microbial genetics, agriculture and bioinformatics.