Enhanced G1 arrest and apoptosis via MDM4/MDM2 double knockdown and MEK inhibition in wild‑type TP53 colon and gastric cancer cells with aberrant KRAS signaling

Murine double minute homolog 2 (MDM2) is an oncoprotein that induces p53 degradation via ubiquitin‑ligase activity. MDM4 cooperates with MDM2‑mediated p53 degradation, directly inhibiting p53 transcription by binding to its transactivation domain. Our previous study reported that the simultaneous inhibition of MDM2 and MDM4 using nutlin‑3 (an inhibitor of the MDM2‑p53 interaction) and chimeric small interfering RNA with DNA‑substituted seed arms...