Neddylation modification regulates lamin B1 expression in breast cancer

Abstract

Background and purpose: The role of neddylation modification in breast cancer has rarely been reported. Previous study found that neddylation modification blocking induced cellular senescence in breast cancer, however, the potential mechanism has not yet been fully elucidated. It is reported that lamin B1 deletion leads to cellular senescence. The purpose of this study was to investigate the correlation between neddylation modification and lamin B1 expression in breast cancer and its possible mechanism. Methods: Neural precursor cell expressed developmentally downregulated protein 8 (NEDD8) and NEDD8-activating enzyme 1 (NAE1), two key proteins of neddylation modification process, in addition to lamin B1 were immunohistochemically stained in tissue microarray from 113 breast cancer patients. The correlation of NEDD8 and NAE1 with lamin B1 was analyzed using Spearman’s rank analysis. The expression of NEDD8 was knocked down to block neddylation modification by CRISPR/Cas9 technique. Western blot assay was used to detect the regulation of lamin B1 by neddylation modification and its mechanisms. Results: Lamin B1 expression was positively correlated with NEDD8 (r=0.817, P<0.000 1) and NAE1 (r=0.406, P<0.000 1) expressions. Blocking neddylation modification by knocking down NEDD8 significantly inhibited the expression of lamin B1. Silencing of p53 partially reversed the inhibition of lamin B1 by neddylation modification blocking. Conclusion: Neddylation modification was positively correlated with lamin B1 expression. Targeting neddylation modification inhibited the expression of lamin B1 in a p53-dependent manner. This study provides new target and clue for the treatment of breast cancer.

Keywords

• |ubiquitin-like|neddylation|lamin b1|breast cancer