BUB1B promotes homologous recombination‑mediated DNA damage repair in breast cancer cells through the PI3K/AKT signaling pathway

Luo,Xuewen; Wei,Yuqin; Lin,Hanxin; Xiao,Ning; Zhao,Wei

doi:10.3892/or.2025.8980

BUB1B promotes homologous recombination‑mediated DNA damage repair in breast cancer cells through the PI3K/AKT signaling pathway

Authors:
- Xuewen Luo
- Yuqin Wei
- Hanxin Lin
- Ning Xiao
- Wei Zhao
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Affiliations: Guangxi Medical University Graduate School, Nanning, Guangxi 530021, P.R. China, Department of Radiation Oncology, The Second Affiliated Hospital of Guangxi Medical University, Nanning, Guangxi 530007, P.R. China
Published online on: September 1, 2025 https://doi.org/10.3892/or.2025.8980
Article Number: 147
Copyright: © Luo et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Radioresistance is a major obstacle to effective radiotherapy in breast cancer. BUB1 mitotic checkpoint serine/threonine kinase B (BUB1B) is involved in numerous biological processes associated with cancer; however, its specific role in mediating radioresistance in breast cancer remains poorly characterized. The present study first evaluated its expression profile and association with patient prognosis through bioinformatics analysis. Subsequently, BUB1B expression in various breast cancer cell lines was validated by reverse transcription‑quantitative PCR. Following short hairpin RNA‑mediated knockdown of BUB1B in MDA‑MB‑231 cells, the impact of BUB1B on the biological functions and radiosensitivity of breast cancer cells was investigated using Cell Counting Kit‑8, colony formation, EdU staining, gap closure, Transwell, immunofluorescence and comet assays, flow cytometric cell cycle analysis, and in vivo xenograft tumor experiments. Downstream signaling pathways regulated by BUB1B were identified via RNA sequencing and western blotting. The results revealed that BUB1B expression was elevated in breast cancer tissues and cell lines, and higher BUB1B expression was associated with poorer prognosis in patients with breast cancer. Functional investigations demonstrated that BUB1B may facilitate the proliferation, invasion and migration of breast cancer cells. Furthermore, BUB1B had a significant influence on the radioresistance of breast cancer, and promoted homologous recombination‑mediated DNA damage repair and cell cycle arrest. At the molecular level, BUB1B may exert its effects through regulation of the PI3K/AKT signaling cascade. In conclusion, these findings indicated that BUB1B may be a potential therapeutic target to overcome radioresistance in breast cancer.

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