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. This evidence concerns the gene LHX1 and esophageal squamous cell carcinoma.