To determine whether other Id genes could compensate for Id1 in this mechanism, we used specific small interfering RNAs (siRNAs) to knock down Id2, Id3 and Id4, respectively, in ESCC cells and found that manipulating the expression of these Id genes had no effect on the expression of IGF2, thus affirming the specificity of Id1 in this process (Supplementary Fig. 1c). This evidence concerns the gene ID4 and esophageal squamous cell carcinoma.