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Background and aims <p>Breast cancer (BRCA) remains one of the most prevalent malignancies and a major threat to women’s health worldwide. The biological role and mechanistic basis of the long non-coding RNA (lncRNA) RERE-AS1 in BRCA remain unclear.</p> Methods <p>Clinical and RNA sequencing data from BRCA patients were analyzed to determine RERE-AS1 expression levels. RNA fluorescence in situ hybridization (FISH) was used to visualize its distribution in tumor tissues. Functional assays were conducted in MCF-7 and T47D cells to assess the effects of RERE-AS1 on cellular proliferation, migration, invasion, and apoptosis using Cell Counting Kit-8 (CCK-8), Transwell assays, and flow cytometry. Cell cycle progression was also evaluated. A co-culture system of BRCA cells and immune cells was established to examine immune cell migration, lactate dehydrogenase (LDH) release, and immune cytotoxicity. Cytokine secretion was quantified via enzyme-linked immunosorbent assay (ELISA). Furthermore, a xenograft mouse model was utilized to confirm the impact of RERE-AS1 on tumor growth and its response to anti-PD-1 therapy.</p> Results <p>RERE-AS1 expression was markedly decreased in BRCA tissues and correlated with overall survival (OS), tumor stage, and immune infiltration levels. Functional experiments demonstrated that RERE-AS1 overexpression inhibited BRCA cell proliferation, migration, and invasion while inducing apoptosis and cell cycle arrest. Additionally, RERE-AS1 strengthened the interaction between BRCA and immune cells, reduced immune escape, and enhanced tumor sensitivity to immune checkpoint blockade therapy.</p> Conclusion <p>RERE-AS1 acts as a promising prognostic biomarker and potential therapeutic target in BRCA. Its expression is closely associated with disease progression and patient outcomes and plays a regulatory role in tumor cell behavior and immune microenvironment modulation.</p> Clinical relevance statement <p>This study identifies RERE-AS1 as a critical regulator of tumor-immune interactions, suggesting its potential for guiding precision immunotherapy and prognostic assessment in BRCA patients.</p> Graphical abstract <p></p>

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RERE-AS1 as a regulator of immune modulation and therapeutic response in breast cancer

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年12月19日

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  • Shaohui Jiang,
  • Weijie He,
  • Zhimin Li,
  • Haodong He,
  • Yuehua Li,
  • Meiling Wen,
  • Hongbo Zhu,
  • Pengfei Luo

摘要

Background and aims

Breast cancer (BRCA) remains one of the most prevalent malignancies and a major threat to women’s health worldwide. The biological role and mechanistic basis of the long non-coding RNA (lncRNA) RERE-AS1 in BRCA remain unclear.

Methods

Clinical and RNA sequencing data from BRCA patients were analyzed to determine RERE-AS1 expression levels. RNA fluorescence in situ hybridization (FISH) was used to visualize its distribution in tumor tissues. Functional assays were conducted in MCF-7 and T47D cells to assess the effects of RERE-AS1 on cellular proliferation, migration, invasion, and apoptosis using Cell Counting Kit-8 (CCK-8), Transwell assays, and flow cytometry. Cell cycle progression was also evaluated. A co-culture system of BRCA cells and immune cells was established to examine immune cell migration, lactate dehydrogenase (LDH) release, and immune cytotoxicity. Cytokine secretion was quantified via enzyme-linked immunosorbent assay (ELISA). Furthermore, a xenograft mouse model was utilized to confirm the impact of RERE-AS1 on tumor growth and its response to anti-PD-1 therapy.

Results

RERE-AS1 expression was markedly decreased in BRCA tissues and correlated with overall survival (OS), tumor stage, and immune infiltration levels. Functional experiments demonstrated that RERE-AS1 overexpression inhibited BRCA cell proliferation, migration, and invasion while inducing apoptosis and cell cycle arrest. Additionally, RERE-AS1 strengthened the interaction between BRCA and immune cells, reduced immune escape, and enhanced tumor sensitivity to immune checkpoint blockade therapy.

Conclusion

RERE-AS1 acts as a promising prognostic biomarker and potential therapeutic target in BRCA. Its expression is closely associated with disease progression and patient outcomes and plays a regulatory role in tumor cell behavior and immune microenvironment modulation.

Clinical relevance statement

This study identifies RERE-AS1 as a critical regulator of tumor-immune interactions, suggesting its potential for guiding precision immunotherapy and prognostic assessment in BRCA patients.

Graphical abstract