Downregulation of lamin B2 is crucial for chromosomal instability and its restoration prevents mitotic defect

Abstract

The majority of human cancer shows abnormal chromosomal content, termed chromosomal instability (CIN). CIN has been recognized to be a direct cause of cancer and elucidation of the mechanism could improve cancer diagnosis and treatment. Chromosome missegregation is a major cause of CIN, although the precise mechanism remains uncertain. Recently, it has been reported that lamin B plays a critical role in spindle assembly, in addition to its structural role in interphase nuclei. Here we provide evidences suggesting that downregulation of lamin B2 is a critical step for CIN in several cancer cell lines. We showed that the expression of lamin B2 was greatly decreased in cell lines with CIN characteristics and lamin B2-knockdown in near diploid MIN (microsatellite instability) cell lines induced mitotic defects such as chromosome missegregation, aneuploidy, and aberrant spindle assembly. Strikingly, ectopic expression of lamin B2 in a CIN cell line prevented these mitotic defects. Our results not only demonstrate that downregulation of lamin B2 contributes to CIN but maintenance of lamin B2 expression level is important for proper mitotic processes and chromosome integrity.