title: Gene expression profiling of replicative and induced senescence.
abstract: Cellular senescence is a cell cycle arrest accompanied by high expression of cyclin dependent kinase inhibitors which counteract overactive growth signals, which serves as a tumor suppressive mechanism. Senescence can be a result of telomere shortening (natural or replicative senescence) or DNA damage resulting from exogenous stressors (induced senescence). Here, we performed gene expression profiling through RNA-seq of replicative senescence, adriamycin-induced senescence, H2O2-induced senescence, and 5-aza-2-deoxycytidine-induced senescence in order to profile the pathways controlling various types of senescence. Overall, the pathways common to all 4 types of senescence were related to inflammation and the innate immune system. It was also evident that 5-aza-induced senescence mirrors natural replicative senescence due to telomere shortening. We also examined the prevalence of senescence-associated secretory phenotype (SASP) factors in the RNA-seq data, showing that it is a common characteristic of all 4 types of senescence. In addition, we could discriminate changes in gene expression due to quiescence during cellular senescence from those that were specific to senescence.
authors.affiliation: a Cancer Biology Program ; Wayne State University School of Medicine.
authors.forename: Maggie
authors.initials: M
authors.lastname: Purcell
authors.forename: Adele
authors.initials: A
authors.lastname: Kruger
authors.forename: Michael A
authors.initials: MA
authors.lastname: Tainsky
mesh_terms: D001374:Azacitidine / Q000031:analogs & derivatives / Q000633:toxicity; D045744:Cell Line, Tumor; D016922:Cellular Senescence / Q000187:drug effects; D056751:Cyclin A2 / Q000235:genetics / Q000378:metabolism; D000077209:Decitabine; D004317:Doxorubicin / Q000633:toxicity; D015870:Gene Expression / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D006861:Hydrogen Peroxide / Q000633:toxicity; D007375:Interleukin-1 / Q000235:genetics / Q000378:metabolism; D017423:Sequence Analysis, RNA
chemical_list: D056751:Cyclin A2; D007375:Interleukin-1; D000077209:Decitabine; D004317:Doxorubicin; D006861:Hydrogen Peroxide; D001374:Azacitidine
keywords: 5-aza, 5-aza-2′-deoxycytidine; 5-aza-2’-deoxycytidine; GGA, Genomatix Genome Analyzer; H2O2, hydrogen peroxide; IFN, interferon; IPA, Ingenuity Pathway Analysis; LFS, Li-Fraumeni Syndrome; LLP, lowest passage; LP, low passage; Li Fraumeni Syndrome; RNA-seq; SPIA, Signaling Pathway Impact Analysis; Senescence; adria, adriamycin; adriamycin; aging; hydrogen peroxide; nat, natural