We further looked at the effect of loss or gain of NOTCH1 gene function on USP5 expression in ESCC cells and found that knockout of NOTCH1 gene significantly suppressed while overexpression of NICD1 significantly enhanced USP5 expression at both RNA and protein levels (Fig. 3f−h, Supplementary Fig. 4d and e). The gene discussed is USP5; the disease is esophageal squamous cell carcinoma.