Table 1.
Mechanisms | Functions | Molecular target | Ref |
---|---|---|---|
Cell cycle | BRD4 inhibition blocks G0/G1 phase | Inhibits G1 gene expression (Ccnd1, Ccnd2, Mcm2, Ranbp1, Nid1, Orc2, Pop1, et al.) | [29], [30], [31] |
G2/M phase | Unknown | [26] | |
BRD4 ectopic expression inhibits G0/G1 phase | Inhibits RFC-dependent DNA elongation | [32] | |
Apoptosis | BRD4 inhibition triggers apoptosis | Downregulates c-Myc | [45] |
Inhibits BRD4-NUT oncogene | [46], [47] | ||
Accumulates RNA-DNA hybrids | [48] | ||
BRD4 inhibition alleviates apoptosis | Inhibits FOXO4-dependent ROS generation through PI3K/AKT pathway | [49] | |
Induces autophagy through MAPK/mTOR/ULK1 pathway | [51] | ||
Cell senescence | BRD4 inhibition induces cell senescence | Blocks telomere elongation | [55] |
Upregulates p21 expression | [57], [58], [59] | ||
BRD4 inhibition alleviates cell senescence | Downregulates SASP-related genes | [67], [68], [64], [65] | |
Induces autophagy via AMPK/mTOR/ULK1 pathway | [51] | ||
SASP | BRD4 inhibition alleviates SASP | Inhibits SASP via SE remodeling | [64] |
Senolysis | ARV-825 and JQ1 provoke senolysis | Attenuates NHEJ and upregulates autophagic gene expression | [70] |
Autophagy | BRD4 inhibition inhibits autophagy | Unknown | [92] |
BRD4 inhibition promotes autophagy | Promotes autophagy and lysosomal biosynthesis through methyltransferase G9a | [82] | |
BRD4 inhibition promotes mitophagy | Activates PINK1/Parkin pathway | [89] | |
Mitochondria dysfunction | BRD4 inhibition promotes mitochondria dysfunction | Increases the levels and activity of OXPHOS protein complexes | [94] |
BRD4 inhibits mitochondria biogenesis | Downregulates PGC-1α gene expression | [97] | |
BRD4 inhibition blocks mitochondria fission | Inhibits MFF expression | [100] | |
BRD4 inhibition increases mitochondria fission | Inhibits c‐Myc and alters mitochondrial dynamics | [39] |
RFC: replication factor C; ROS: reactive oxygen species; SASP: senescence-associated secretory phenotype; NHEJ: non-homologous end joining; OXPHOS: oxidative phosphorylation; MFF: mitochondrial fission factor.