Time-resolved miRNA-mRNA integrated analysis reveals the miRNA-mRNA networks underlying plasma membrane damage-dependent senescence and DNA damage response-dependent senescence in WI-38 normal human fibroblasts

Cellular senescence is a stable cell cycle arrest associated with upregulated inflammatory responses. Senescent cells contribute to various pathological and physiological processes including organismal aging and cancer. Cellular senescence can be induced by various cellular stresses including DNA damage, telomere shortening, oncogene activation, and epigenetic alterations. We have shown that plasma membrane damage can also induce cellular senescence. However, common and specific molecular mechanisms among different senescent cell subtypes remain unknown. MicroRNAs (miRNAs) regulate mRNA and rewire gene expression profiles, contributing to multiple processes including cellular senescence. Here, we performed time-resolved miRNA sequencing and compared the results with mRNA sequencing results using cells experiencing plasma membrane damage-dependent senescence (PMD-Sen) and cells undergoing DNA damage response-dependent senescence (DDR-Sen). Overall design: miRNA sequencing of proliferating and senescence-induced WI-38 cells. Two biological replicates were analyzed for each of 4 conditions (Young proliferating, SDS-treated, DXR-treated, and replicative senescence); SDS-treated and DXR-treated cells were collected at Day 0, 1, 2, 3, 4, 6, 8 and 16 after removal of SDS or DXR.