Analysis of previously reported BRD4 target genes related to mitochondrial function in senescent fibroblasts.

Because BRD4, a major target of ARV825, has been implicated in the regulation of mitochondrial gene expression in cardiomyocytes (DOI: 10.1161/CIRCULATIONAHA.120.047239), we examined whether ARV825-induced cell death in senescent cells is attributable to changes in the expression of mitochondria-related genes. Although senescent cells were eliminated within two days of ARV825 treatment, the mRNA expression levels of mitochondrial-related genes remained unchanged. In contrast, XRCC4— which functions together with DNA ligase IV in non-homologous end joining and has been reported to regulate senolysis (DOI: 10.1038/s41467-020-15719-6)— was downregulated, consistent with previous findings. Overall design: RNA-seq profiling of doxorubicin-induced senescent TIG-3 cells with ARV825 or vehicle (DMSO) for 2days.