Temporal regulation of gene expression and pathways in chemotherapy-induced senescence in HeLa cervical cancer cell line

Abstract

Cellular senescence is the state of permanent growth arrest. Chemotherapeutic drugs induce senescence, known as therapy-induced senescence. Although there are studies deciphering processes in senescence, more studies providing detailed information on therapy-induced senescence at the transcriptome level are needed. In order to understand temporal molecular changes of doxorubicin treatment in the course of senescence formation, two data sets from HeLa cells at 16 h and 72 h doxorubicin treatment were analyzed. GO BP enrichment, KEGG pathways and hub genes specific to or shared between 16 h and 72 h doxorubicin treated HeLa cells were identified. Genes functioning in p53 signaling were upregulated only in 16 h, while genes functioning in extracellular matrix organization were upregulated only in 72 h doxorubicin treated HeLa cells. Wound healing genes were gradually upregulated from 16 h to 72 h doxorubicin treatment and metabolic pathways were downregulated at both. ncRNA processing and ribosome biogenesis GO BP terms were enriched in upregulated genes at 16 h, while these terms were enriched in downregulated genes at 72 h senescent HeLa cells. According to our results, genes functioning in p53 signaling may be involved in the induction of senescence, but may not be required to maintain senescence in HeLa cells.