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RANBP1 promotes immune evasion in triple-negative breast cancer by suppressing T cell infiltration via the
Pengxia Song1, Xianglin Liu2, Huiping Qiu1
1Medical School, Quzhou College of Technology, No.18, Jiangyuan Road, Quzhou, 324000, Zhejiang, PR China.
Background:
T cell dysfunction in the tumor microenvironment (TME) is a major obstacle to effective immunotherapy in triple-negative breast cancer (TNBC). The molecular mechanisms underlying T cell exclusion remain poorly understood.
Purpose:
This study identifies RANBP1 as an oncogenic factor in TNBC and investigates its role in modulating T cell infiltration and tumor progression.
Methods:
Single-cell and bulk RNA sequencing were used to assess immune cell infiltration associated with RANBP1 expression. RANBP1 protein levels were evaluated in 87 TNBC tumor and adjacent normal tissues by immunohistochemistry. Kaplan-Meier analysis was used to assess overall survival. In vitro and in vivo assays were performed to explore the RANBP1/miR-769-5p/PRUNE2 pathway.
Results:
scRNA-seq identified 10 cell types in the TNBC TME. High RANBP1 expression correlated with increased tumor cells, B cells, macrophages, and epithelial cells, and reduced T cells. Cell-cell communication was enhanced in the high-RANBP1 group. TCGA and GSE65194 data confirmed decreased CD4⁺ T cells and Tregs in high-RANBP1 tumors. RANBP1 was significantly upregulated in TNBC and associated with poor prognosis. Functional studies showed that RANBP1 promotes TNBC cell proliferation and migration. Mechanistically, RANBP1 upregulates oncogenic miR-769-5p, which suppresses PRUNE2, a tumor suppressor that normally inhibits TNBC progression.
Conclusions:
RANBP1 shapes an immunosuppressive microenvironment in TNBC by reducing T cell infiltration through the miR-769-5p/PRUNE2 axis. These findings reveal a novel immune escape mechanism and suggest that targeting RANBP1 may enhance immunotherapy efficacy in TNBC.
Insights
RAN binding protein 1 (RANBP1) promotes triple-negative breast cancer (TNBC) progression by reducing T cell infiltration. Targeting RANBP1 may improve immunotherapy outcomes in TNBC patients.
Area of Science:
- Oncology
- Immunology
- Molecular Biology
Background:
- T cell dysfunction in the tumor microenvironment hinders immunotherapy for triple-negative breast cancer (TNBC).
- Molecular mechanisms of T cell exclusion in TNBC are not well understood.
Purpose of the Study:
- Identify RAN binding protein 1 (RANBP1) as an oncogenic factor in TNBC.
- Investigate RANBP1's role in T cell infiltration and tumor progression.
Main Methods:
- Utilized single-cell and bulk RNA sequencing to analyze immune cell infiltration.
- Performed immunohistochemistry on TNBC tissues to quantify RANBP1 expression.
- Conducted in vitro and in vivo assays to elucidate the RANBP1/miR-769-5p/PRUNE2 pathway.
Main Results:
- High RANBP1 expression correlated with increased tumor cells and immune cells (B cells, macrophages), but reduced T cells.
- RANBP1 upregulation in TNBC is linked to poor prognosis and promotes cancer cell proliferation and migration.
- Mechanistically, RANBP1 upregulates miR-769-5p, suppressing the tumor suppressor PRUNE2.
Conclusions:
- RANBP1 creates an immunosuppressive TNBC microenvironment by decreasing T cell infiltration via the miR-769-5p/PRUNE2 pathway.
- This study reveals a novel immune escape mechanism in TNBC.
- Targeting RANBP1 presents a potential strategy to enhance immunotherapy efficacy for TNBC.
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