# RANBP1 promotes immune evasion in triple-negative breast cancer by suppressing T cell infiltration via the miR-769-5p/PRUNE2 axis

## TL;DR

This study shows that RANBP1 helps triple-negative breast cancer avoid immune attacks by reducing T cell presence through a specific molecular pathway.

## Contribution

The study identifies a novel RANBP1/miR-769-5p/PRUNE2 axis that promotes immune evasion in triple-negative breast cancer.

## Key findings

- High RANBP1 expression correlates with reduced T cell infiltration in triple-negative breast cancer.
- RANBP1 promotes tumor growth and migration by upregulating miR-769-5p and suppressing PRUNE2.
- Targeting RANBP1 may improve immunotherapy outcomes in triple-negative breast cancer.

## Abstract

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.

This study identifies RANBP1 as an oncogenic factor in TNBC and investigates its role in modulating T cell infiltration and tumor progression.

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.

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.

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.

The online version contains supplementary material available at 10.1007/s12672-025-03872-7.