Abstract PS4-02-15: Sumo e3 ligase ranbp2 affects triple-negative breast cancer tumorigenicity by stabilizing birc5 expression

Abstract Background: Triple-negative breast cancer (TNBC) is more aggressive and has higher metastasis rate compared with other subtypes of breast cancer. RAN binding protein 2 (RANBP2) is a less-explored SUMO E3 ligase and has been shown to play key roles in various cellular cycle processes. However, its biological function and molecular mechanism in TNBC remain largely unclear. Methods: RANBP2 expression was evaluated in TNBC patients’ s tumor tissues with public database and immunohistochemical staining methods. Correlation between RANBP2 expression and patients’ prognosis was also analyzed. The effects of RNABP2 on TNBC cell proliferation ability were detected by CCK-8, colony formation, apoptosis and cell cycle analysis. Tumor formation assay was constructed to examine the effects of RANBP2 on TNBC growth in vivo. Proteomic profiling, Western blot, protein stability tests and rescue experiments were further applied to evaluate the detailed mechanism. Results: The expression of RANBP2 was indicated to be upregulated in TNBC tumor tissues and high expression of RANBP2 was correlated with poor prognosis of TNBC patients. Functional studies demonstrated that RANBP2 overexpression promoted TNBC cell proliferation both in vitro and in vivo, whereas RANBP2 knockdown inhibited proliferation, induced apoptosis, and caused G1-S phase cell cycle arrest. Baculoviral IAP Repeat Containing 5 (BIRC5) was identified as a downstream effector of RANBP2. Mechanistically, RANBP2 post-translationally regulated BIRC5 by facilitating its degradation via the proteasomal pathway. Functional rescue experiments further demonstrated that BIRC5 overexpression could partially reverse the anti-proliferative effects induced by RANBP2 knockdown in TNBC cells. Conclusion: RANBP2 serves as a critical regulator of TNBC development and progression. Targeting RANBP2/BIRC5 axis may provide new insights into therapeutic strategies and research directions for TNBC treatment. Citation Format: Y. Lin, J. Wu, Y. Li, F. Fu, C. Wang. Sumo e3 ligase ranbp2 affects triple-negative breast cancer tumorigenicity by stabilizing birc5 expression [abstract]. In: Proceedings of the San Antonio Breast Cancer Symposium 2025; 2025 Dec 9-12; San Antonio, TX. Philadelphia (PA): AACR; Clin Cancer Res 2026;32(4 Suppl):Abstract nr PS4-02-15.