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

[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.