This finding is consistent with the “core transcription regulatory circuitry (CRC)” paradigm that is prevalent across diverse cell types.[31, 32] More importantly, inhibiting UHRF1 in conjunction with disrupting DNA methylation activity effectively dampened the epigenetically activated UHRF1/NKX2‐5/LHX1 feedback loop, thereby inhibiting ESCC growth. The gene discussed is NKX2-5; the disease is esophageal squamous cell carcinoma.