Lamin B1 facilitates tumour progression through RAD51-mediated homologous recombination repair in estrogen receptor-positive breast cancer

The prognostic value and biological functions of Lamin B1 in breast cancer are poorly understood. Here, we aim to investigate the effect of Lamin B1 on breast cancer and the underlying mechanisms. We demonstrate that Lamin B1 expression is significantly increased in breast tumour tissues. High expression of Lamin B1 is correlated with advanced histological grade ( P  = 0.015), low estrogen receptor (ER) expression ( P  = 0.001) and low progesterone receptor (PR) expression ( P  = 0.04). High Lamin B1 expression is significantly correlated with decreased overall survival (OS) time of breast cancer in the total cohort ( P  = 0.022) and ER-positive cohort ( P  = 0.016), but not in the ER-negative cohort ( P  = 0.704). In addition, high Lamin B1 expression is found to be an independent predictor of poor OS. Importantly, Lamin B1 overexpression promotes ER-positive breast tumour growth in vitro and in vivo . Mechanistically, Lamin B1 promotes tumour progression through RAD51-dependent homologous recombination (HR) repair. Moreover, Lamin B1 upregulates RAD51 expression both at transcriptional and post-translational levels. Taken together, the results suggest that high Lamin B1 expression plays a vital role in breast cancer growth by promoting RAD51-dependent HR repair, which highlights a potential of Lamin B1/RAD51 axis as a therapeutic target for the clinical treatment of breast cancer.