MiR-96-5p expression is sufficient to induce and maintain the senescent cell fate in the absence of stress.

ABSTRACT: Senescence is a cell fate driven by different types of stress that results in exit from the cell cycle and expression of an inflammatory senescence-associated secretory phenotype (SASP). Here, we demonstrate that stable overexpression of miR-96-5p was sufficient to induce cellular senescence in the absence of genotoxic stress, inducing expression of certain markers of early senescence including SASP factors while repressing markers of deep senescence including LINE-1 and type 1 interferons. Stable miR-96-5p overexpression led to genome-wide changes in heterochromatin followed by epigenetic activation of p16^Ink4a, p21^Cip1, and SASP expression, induction of a marker of DNA damage, and induction of a transcriptional signature similar to other senescent lung and endotheli

SUBMITTER: Santiago FE 

PROVIDER: S-EPMC11459134 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature