Role of nuclear lamins in modulating circadian gene expression in cancer cells

Abstract

Circadian clocks drive the rhythmic expression of ~5-15% of expressed genes in mammals in a cell-type and tissue-specific manner. Nuclear envelope, a global regulator of the genome, interact with the circadian core-clock transcription factor BMAL1 through Man1. LBR and lamin B1 were also found to have similar regulatory roles as Man1 in regulating rhythmic gene expression. We hypothesize that B-type lamins and especially lamin B2 might modulate and have regulatory roles in clock function. Further studies also show that the expression profiles of the circadian genes differ in human colorectal cells from that of mouse embryonic fibroblasts (MEFs). Therefore clock disruption in MEFs may not be translated to clock disruption in human colorectal cancer cells. We also find that while AKT2 and KRAS show fluctuations in their expression levels across time, SNAI1 and RUNX2 levels are relatively constant. The nuclear envelope is likely to associate and regulate core circadian clock genes and maintain the periodicity of clock-controlled genes in cells.