Lamin B2 Promotes The Malignant Phenotype Of Non-small Cell Lung Cancer Cells By Upregulating Dimethylation Of Histone 3 Lysine 9

Objectives: The relationship between Lamin B2,a member of the lamin family,and tumor proliferation and migration and the underlying mechanism remain unclear.Here we clarify the impact of Lamin B2 on non-small cell lung cancer(NSCLC)cells proliferation and migration,and the underlying mechanism.Methods: Tissue microarray immunohistochemical was used to clarify Lamin B2 expression and the relationship between it and clinicopathological factors in non-small cell lung cancer tissues.Western blotting,immunofluorescence experiments and database analysis were used to investigate the effects of Lamin B2 on different pathway.And to explore the effects of Lamin B2 on tumor cells proliferation and migration,more cytological experiments,such as transwell assay,were conducted to the tumor cells lines.We conducted co-immunoprecipitation,chromatin immunoprecipitation(ChIP),to explore the molecular mechanism underneath,and demonstrate the conclusion by rescue experiments.Results:1.The expression of Lamin B2 in NSCLC was higher than that in normal tissues,and the high expression of Lamin B2 was often accompanied by high TNM stage and lymph node metastasis.Lamin B2 was distributed on the inner side of cell nuclear membrane and nucleolus.2.Overexpression of Lamin B2 could promote the proliferation and migration of lung cancer cell lines,while interferenced with Lamin B2 could inhibit the proliferation and migration of lung cancer cells.3.There was a positive correlation between Lamin B2 expression and lysine demethylation at the ninth site of histone H3 in NSCLC.Overexpressed Lamin B2 in lung cancer cell lines,the level of lysine dimethylation at the ninth site of histone H3 increased.4.In non-small cell lung cancer cells,Lamin B2 could be combined with Cyclin D1 to promote the G9 a expression,the H3K9 specific methyltransferase,to play a role in promoting histone methylation.5.When Lamin B2 was highly expressed,H3K9me2 was enriched in the(-1997～-1730)and(-1090～-937)regions of the E-cadherin gene promoter and inhibited E-cadherin gene transcription and promoted cancer cell migration.Conclusions: Our study proves that Lamin B2 was highly expressed in NSCLC cells and promotes their migration ability by promoting H3K9me2,which induces E-cadherin gene silencing.