The Rules Of Menin Regulates Cellular Senescence

"Cell senescence" refers to the state wherein a cell undergoes permanent growth arrest in response to various cellular stresses.It is a natural barrier to tumorigenesis,and it plays an important role in aging,fibrosis and tissue repair.DNA damage is a key event leading to senescence,which may be associated with telomere dysfunction,activation of p53-p21 senescence pathway and p16/P-Rb pathway,and accompanied with the expression of senescence-associated secretory phenotype(SASP).menin is an important nuclear protein which is expressed in many tissues and has many functions.It participates in the regulation of multiple transcription factors,signal transduction and tumor pathways.Recently it has reported that menin regulates CD4-T cell's senescence by maintaining the expression of Bach2,which suggested that senescence is one of the important cellular phenotypes regulated by menin.However,the mechanisms and biological significance of menin regulating cell senescence have not been fully confirmed.This study respectively use mouse embryonic fibroblast(MEF)and lung cancer cells as research objects,established cellular senescence models which induced by ionizing radiation,investigated the rules of menin regulated cellular senescence in different cells.Our study found that menin promotes cellular senescence in MEF cells,mainly by significantly inhibiting Tert activity and promoting p16 transcription.In lung cancer cells,menin regulates cellular senescence in different ways:in small cell lung cancer cell line NCI-H446,menin promotes cellular senescence by maintaining p16 expression and inhibiting p-Rb level.In non-small cell lung cancer cell line A549,menin inhibits cellular senescence mainly by inhibiting related genes transcription of senescence associated secretory phenotype(SASP).In summary,menin is involved in regulating cellular senescent phenotypes of normal cells and tumor cells through various mechanisms.This study has stated the different rules of menin regulate cellular senescence in different cell models,and investigated the mechanisms of menin mediated cellular senescent phenotype.It provides new ideas for the study of menin's regulation in some aging associated diseases,and provides a new theoretical basis for the mechanism of menin participate in tumor development.