Targeting ACE2-BRD4 crosstalk in colorectal cancer and the deregulation of DNA repair and apoptosis.
Shilan ZhangSabeeta KapoorChakrapani TripathiJorge Tovar PerezNivedhitha MohanWan Mohaiza DashwoodKe ZhangPraveen RajendranRoderick Hugh DashwoodPublished in: NPJ precision oncology (2023)
ACE2 overexpression in colorectal cancer patients might increase susceptibility to SARS-CoV-2 infection. We report that knockdown, forced overexpression, and pharmacologic inhibition in human colon cancer cells targeted ACE2-BRD4 crosstalk to mediate marked changes in DNA damage/repair and apoptosis. In colorectal cancer patients for whom high ACE2 plus high BRD4 expression is predictive of poor survival, pan-BET inhibition would need to consider proviral/antiviral actions of different BET proteins during SARS-CoV-2 infection.
Keyphrases
- dna repair
- dna damage
- angiotensin converting enzyme
- oxidative stress
- angiotensin ii
- endoplasmic reticulum stress
- cell cycle arrest
- cell proliferation
- cell death
- cancer therapy
- endothelial cells
- poor prognosis
- respiratory syndrome coronavirus
- dna damage response
- long non coding rna
- induced pluripotent stem cells
- drug delivery
- signaling pathway
- pluripotent stem cells
- free survival