Screening And Identification Of Tumor Cellular Senescence-related Genes

Cellular senescence, an irreversible cell cycle arrest, is a limited proliferative state inwhich cells are induced by external stimuli or aberrant expression of genes. It has beenproven that tumor cells can escape from the senescence program and then undergo malignantproliferation. Cellular senescence is therefore an effective mean of tumor-suppressionmechanism.Epigenetic modifications play a key role in the senescence process. To identify newgenetic events controlling senescence, we employed a specific loss-of-function screeningstrategy using a synthetic siRNA library in MDA-MB-231human breast cancer cells. Afterthe initial screening, we obtained7positive candidate genes. In order to study the roles ofthese genes in the tumor cellular senescence, we focused on the siRNAs that target the genesof RAD21, CARM1and TRIM28for further studying the effects of the interference of thesegenes on the morphological changes and cellular senescence in MDA-MB-231cells. Weshow that transfection of RAD21siRNA, CARM1siRNA and TRIM28siRNA can result inthe appearance of senescence, including proliferation inhibition, and enhanced senescence-associated-β-galactosidase activity. Simultaneously, our results demonstrate that knockdownof RAD21, CARM1by RNA interference in human breast cancer MDA-MB-231cellspromote the formation of heterochromatin foci.This work has provided important data for further insights into the mechanisms of thefunctions of these three genes in cellular senescence in tumor cells. It is also crucial to thedevelopment of new therapeutic strategies based on the induction of the tumor cellularsenescence.