Effect of lamin-A expression on migration and nuclear stability of ovarian cancer cells

Abstract Objective Nuclear lamina plays important roles in nuclear shape and mechanical stability. Many studies demonstrated that defects of lamin-A were associated with several diseases, but little research was found on its potential roles in ovarian cancer. Methods GEPIA and GEO database were used to analyze lamin-A in ovarian tissues, followed by assessing lamin-A and prognosis of ovarian cancer patients with Kaplan-Meier plotter. Then, transient transfected HO-8910 cells with shRNA to knockdown lamin-A. Knockdown efficiency was determined by western blot, qRT-PCR and immunofluorescence. Meanwhile, lamin-A was overexpressed in HO-8910 PM cells. Then, 2D migration, 3D migration through 3 μm and 8 μm pores were carried out, followed by immunofluorescence and TEM observation. Results Lamin-A tended to be lower in ovarian cancer, and higher expression of lamin-A was associated with better survival. After lamin-A knockdown, 2D and 3D migration (3 μm, 8 μm) abilities of HO-8910 cells were significantly increased ( p Conclusions Lamin-A was down-regulated in ovarian cancer, and higher lamin-A was associated with better prognosis. Nuclei with high lamin-A were severely deformed through constricted pores. Moderate lamin-A enhanced nuclear plasticity, so as to strengthen migration ability. When lamin-A was further knockdown, ovarian cancer cells that migrated through restricted pores decreased, with DNA damage, genomic instability and impairment of DNA damage repair.